Jutti Levita | University of Padjadjaran (UNPAD) (original) (raw)

Books by Jutti Levita

Research paper thumbnail of Pemodelan Molekul dalam Kimia Medisinal

This book discusses about the simple basics of molecular modeling which is easily to be understoo... more This book discusses about the simple basics of molecular modeling which is easily to be understood by beginners. It also explains about ligand representation, analysis of binding pocket, interaction of ligand and macromolecule, and the relationship between molecular modeling with in vitro and in vivo studies. Informations concerning molecular modeling freewares are also provided.

Some examples written in this book are based on the author’s experimental results which have been published in journals or presented in seminars.

Papers by Jutti Levita

Research paper thumbnail of Discovering Inhibitors of Tyrosinase Enzyme from Zingiberaceae for Depigmentation Agents

Tyrosinase enzyme, which has two copper ions in its catalytic site, involved in skin pigmentation... more Tyrosinase enzyme, which has two copper ions in its catalytic site, involved in skin pigmentation by catalyzing three oxidation reactions on melanogenesis, that are conversion of L-tirosine to L-DOPA, L-DOPA to dopaquinone, and 5,6-dihydroxyindole to 5,6-indolequinone. An inhibition of melanogenesis was proven in vitro by bioactive compounds of Zingiberaceae plants, which are ethyl p-metoxycinnamate, galangin (IC50 10 μM), 6-gingerol (IC50 25-100 μM), 4-hydroxypanduratin-A (IC50 23.2 μM), isopanduratin-A (IC50 10.6 μM), kaempferol (IC50 0.23 μM), and kaempferida. In this paper we studied the interaction of these compounds with tyrosinase enzyme using AutoDock Vina. The interactions were then compared to arbutin (hydroquinone-β-D-glucoside), kojic acid, and hydroquinone, that have been well known as depigmentation agents in cosmetics. All bioactive compounds of Zingiberaceae plants were able to interact with tyrosinase. Compared to others, kaempferol showed the lowest inhibition constant value (Ki 2.7 µM) and two metal interactions with both copper ions, Cu501 and Cu502, which means that this compound was predicted as the strongest inhibitor of tyrosinase enzyme. Kaempferol interacted with tyrosinase by blocking the entrance of the enzyme’s catalytic site, therefore it will prevent the substrate to react with the enzyme. It can be concluded that bioactive compounds of Zingiberaceae can be developed as an inhibitors of tyrosinase.

Research paper thumbnail of In silico study of andrographolide as protease inhibitors for antimalarial drug discovery

Malaria parasite encodes several homologues of aspartic proteases such as plasmepsin I, II and IV... more Malaria parasite encodes several homologues of aspartic proteases such as plasmepsin I, II and IV which are responsible for degradation of host erythrocyte hemoglobin inside the parasite’s food vacuole, hence plasmepsins are novel targets for antimalarial drug discovery. Previous study concluded that Andrographis paniculata herbs extract has been proven to exert antimalarial activity. The molecular mechanism of this activity was not described. The objective of this paper was to investigate the interaction between andrographolide, a major constituent of Andrographis paniculata with the ligand binding domain of plasmepsin I, II and IV, to find the most favorable binding site as well as to predict the binding mode. Pepstatin, a protease inhibitor, was used as the standard. Docking studies showed that pepstatin gave better binding interactions to plasmepsin I, II and IV with binding affinity and inhibition constant values Ei = -10.3 kcal/mol; Ki = 0.02 uM (plasmepsin I), Ei = -8.9 kcal/mol; Ki = 0.3 uM (plasmepsin II), Ei = -9.3 kcal/mol; Ki = 0.15 uM (plasmepsin IV), respectively while andrographolide showed Ei = -9.8 kcal/mol; Ki = 0.07 uM (plasmepsin I), Ei = -8.7 kcal/mol; Ki = 0.42 uM (plasmepsin II), Ei = -8.8 kcal/mol; Ki = 0.35 uM (plasmepsin IV). According to the result, we concluded that andrographolide could be developed as protease inhibitor for antimalarial drug.

Research paper thumbnail of Computational Study of Triterpenoids of Ganoderma lucidum with Aspartic Protease Enzymes for Discovering HIV-1 and Plasmepsin Inhibitors

Rapid resistance development of HIV-1 and Plasmodium falciparum parasite requires discovery of mo... more Rapid resistance development of HIV-1 and Plasmodium falciparum parasite requires discovery of more potent new drugs. Aspartic protease enzymes expressed by HIV-1 and Plasmodium falciparum could be used as important drug targets. The catalytic site is located at the bottom of a cleft in the enzyme surface and consists of two aspartic acids. Aspartic proteases are inhibited by pepstatin-A, a naturally occurring peptide containing two statins, which replace the amino acids. The hydroxyl group of the statine binds tightly to the catalytically-active aspartic acid residues in the active site of protease, thereby mimicking the transition state of the peptide cleavage. Previous study proved that ganoderiol-F, a triterpenoid isolated from the stem of Ganoderma sinense showed higher affinity towards HIV-1 protease (binding energy= -11.40 kcal/mol and Ki= 4.68 nM) than to plasmepsin I (binding energy= -9.96 kcal/mol and Ki= 50.94 nM). In this paper, computational studies of triterpenoids from Ganoderma lucidum with the catalytic site of HIV-1 protease and plasmepsin I, were performed using AutoDock 4.2. Nelfinavir and KNI-10006 were used as the standards for HIV-1 protease and plasmepsin I, respectively. The four compounds are able to interact with both enzymes. Ganoderat acid-B showed the best affinity to HIV-1 protease (binding energy= -7.49 kcal/mol and Ki= 0.001 mM) which is better than nelfinavir. Furthermore, the best affinity to Plasmepsin I is showed by ganodermanondiol (binding energy= -7.14 kcal/mol and Ki= 0.005 mM which is better than KNI-10006. According to the values of binding energy and inhibition constant, triterpenoids from Ganoderma lucidum could be developed further as both anti-HIV and anti-malaria.

Research paper thumbnail of BIOAVAILABILITY STUDY OF SAMBILOTO (Andrographis paniculata) HERBS INFUSION IN RABBIT

Andrographis paniculata or sambiloto is one of the most widely used medicinal herbs in Indonesia.... more Andrographis paniculata or sambiloto is one of the most widely used medicinal herbs in Indonesia. The main bioactive chemical constituent, andrographolide, has been reported to have various pharmacological activities. Besides its function for medical purposes, the sambiloto herbs infusion is frequently taken to maintain health. This study was conducted to determine the bioavailability of sambiloto herbs infusion in rabbit plasma, stomach, and liver, calculated as total andrographolide. Fourteen male New Zealand white rabbits were used in this study. Sambiloto herbs infusions were administered orally at the dose 7.04mL/kg body weight to each rabbit. Blood samples were taken at intervals 0.0; 0.5; 1.5; 2.0; 3.0; and 5.0h after infusion administration. Sambiloto herbs infusion, which calculated as andrographolide, levels in plasma, stomach, and liver were analyzed by high performance liquid chromatography using C-18 column as stationary phase and a mixture of methanol-double distilled water (60:40) as mobile phase. Bioavailability parameters obtained were Cmax 0.5549µg/mL (in stomach), 0.2136µg/mL (in plasma), 0.0051µg/mL (in liver); while tmax 1h (in stomach), 1.5h (in plasma), 2h (in liver); and AUC 1.7451µg.h/mL (in stomach), 0.434µg.h/mL (in plasma), 0.0038µg.h/mL (in liver). These data showed that in healthy animals, sambiloto herbs infusion was fastly absorbed from the stomach, distributed in the circulation system, and metabolized in the liver, in subsequent process. Sambiloto herbs infusion showed good bioavailability in rabbit.

Research paper thumbnail of Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer

Nonivasive diagnosis of cancer can be provided by molecular imaging using hybrid modality to obta... more Nonivasive diagnosis of cancer can be provided by molecular imaging using hybrid modality to obtain better sensitivity, specificity and depiction localization of the disease. In this study, we developed a new molecular imaging agent, radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab in the form of 147Gd-DOTA-PAMAM G3.0-trastuzumab, that can be both target-specific radiopharmaceutical in SPECT as well as targeted contrast agent in MRI for the purpose of diagnosis of HER-2 positive breast cancer. 147Gd radionuclide emits γ-rays that can be used in SPECT modality, but because of technical constraint, 147Gd radionuclide was simulated by its radioisotope, 153Gd. Gd-DOTA complex has also been known as good MRI contrast agent. PAMAM G3.0 is useful to concentrate Gd-DOTA compelexes in large quantities, thus minimizing the number of trastuzumab molecules used. Trastuzumab is human monoclonal antibody that can spesifically interact with HER-2. Synthesis of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab was initiated by conjugating DOTA NHS ester ligand with PAMAM G3.0 dendrimer. The DOTA-PAMAM G3.0 produced was conjugated to trastuzumab molecule and labeled with 153Gd. Characterization DOTA-PAMAM G3.0-trastuzumab immunoconjugate was performed using HPLC system equipped with SEC. The formation of immunoconjugate was indicated by the shorter retention time (6.82 min) compared to that of trastuzumab (7.06 min). Radiochemical purity of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab was >99% after purification process by PD-10 desalting column. Radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab compound was stable at room temperature and at 2–8 0C as indicated by its radiochemical purity 97.6 ± 0.5%–99.1 ± 0.5% after 144 h storage.

Research paper thumbnail of Determination of Safrole in Ethanol Extract of Nutmeg (Myristica fragrans Houtt) using RP-HPLC

Dehydrodiisoeugenol (DDIE), myristicin, and safrole are chemical compounds contained in fruit and... more Dehydrodiisoeugenol (DDIE), myristicin, and safrole are chemical compounds contained in fruit and seed of nutmeg (Myristica fragrans Houtt). DDIE shows antidiabetic activity on PPARγ receptor, while myristicin is hallucinogenic agent. Of the three compounds, safrole is the most toxic substance due to its carcinogenic activity. In this work, we developed an analytical method to determine safrole in ethanol extract of nutmeg. Reversed-Phase High Performance Liquid Chromatography (Dionex Ultimate 3000) using C-18 LiChroCART 250-4, LiChrospher 100 RP 18e (5 µm) 250 mm column as stationary phase, was selected as the method of analysis. A mixture of methanol:water (73:27) at flow rate 1 mL/min was used as mobile phase. Detection was done at 282 nm. Using such conditions, retention time for safrole was 10.45 minutes. The recovery was 101.421%, while the value of CV was 0.838%. LOD and LOQ were 0.668 µg/mL and 2.023 µg/mL, respectively. Mean concentration of safrole in the nutmeg seed extract was 10.979%.

Research paper thumbnail of Molecular Modeling Study of PPAR-gamma Agonists: Dehydro-Di-Isoeugenol, Macelignan, Pioglitazon, Netoglitazon, Rosiglitazon as Antidiabetic Drugs

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated trasncription factor... more The peroxisome proliferator-activated receptors (PPARs) are ligand-activated trasncription factors belonging to the nuclear receptor family. The objective of this study is to analyze the molecular aspects of PPARγ agonists which used to design of new antidiabetic drugs. The analysis method was comparing the interactions of ligands in the ligand binding domain of the PPARγ. This analysis showed that most known agonists of PPARγ interacted via hydrogen bond with Tyr473. Pioglitazone showed three hydrogen bonds with His323 and Tyr473. Netoglitazone showed four hydrogen bonds with Ser289, His323, His449, and Tyr473. Rosiglitazone showed five hydrogen bonds with Ser289, His323, His449, and Tyr473. AZ72, an agonist of PPARα and γ showed five hydrogen bonds with Ser289, His323, His449, and Tyr473. Molecular modeling was performed by redocking pioglitazone and rosiglitazone using AutoDock Vina. Docking showed that both pioglitazone (Ki 0.22 μM) and rosiglitazone (Ki 0.70 μM) occupied their origin sites and interacted with Tyr473. Docking simulation was also performed between dehydro-di-isoeugenol and macelignan to visualize the interaction with PPARγ. These two compounds are found in nutmeg's seed (Myristica fragrans Hout) that have been proven had antidiabetic activity in vitro. It can be concluded that agonists of PPARγ should have hydrogen bond donor and acceptor groups for interacting with Tyr473. Tyr473 might be a critical site of interaction between the PPARγ ligand binding domain and its agonists.

Research paper thumbnail of INTERACTIONS OF GANODERIOL-F WITH ASPARTIC PROTEASES OF HIV AND PLASMEPSIN  FOR ANTI-HIV AND ANTI-MALARIA DISCOVERY

International Journal of Pharmacy and Pharmaceutical Sciences, Jun 3, 2014

Objective: HIV-1 has been a killer disease since two decades ago, while a potential cure has not ... more Objective: HIV-1 has been a killer disease since two decades ago, while a potential cure has not yet discovered due to the fast mutations of the HIV-1 enzymes,i.e reverse transcriptase, integrase, and protease. Apart of HIV-1, malaria has been the biggest cause of death in human and it is mostly found in the East part of Indonesia. There are some enzymes in the food vacuole of Plasmodium falciparum which are the targets of anti-malaria discovery, e.g. plasmepsin I, II, IV, and histo-aspartic protease (HAP). Both plasmepsin and HIV-1 protease are aspartic proteases, therefore a single drug could be designed to inhibit both enzymes. Ganoderiol-F is a triterpenoid isolated from the stem of Ganodermasinensewhich shows inhibition on HIV-1 protease with IC50 20-40 μM.

Research paper thumbnail of Structure-based in silico study of 6-gingerol, 6-shogaol, and 6-paradol, active compounds of  ginger (Zingiber officinale) as COX-2 inhibitors

International Journal of Chemistry, Jun 6, 2013

Ginger's (Zingiber officinale) phenolic compounds, that are 6-gingerol, 6-shogaol, and 6-paradol,... more Ginger's (Zingiber officinale) phenolic compounds, that are 6-gingerol, 6-shogaol, and 6-paradol, have been proven to show anti-inflammatory activity. The purpose of this paper was to discover whether these compounds are potential to be used as COX-2 inhibitors through structure-based in silico study, which is based on the character of the receptor. Docking was performed to the binding pockets of both COX-1 and COX-2 enzymes, to examine their selective character on COX-2. The binding pockets used in this project were the sites where flurbiprofen and SC-58, crystallized in the enzymes. The scoring value of the interaction of 6-gingerol, 6-shogaol, and 6-paradol with COX-1 were -7.40, -7.27, and -7.20 kcal/mol, while with COX-2 were -7.97, -8.10, and -7.80 kcal/mol, respectively. K i value to COX-1 were 3.78, 4.66, and 5.30 μM, while to COX-2 were 1.46, 1.16, and 1.93 μM, respectively. We also calculated the selectivity index value of these compounds to COX-2 and resulted an interval of 0.2 to 0.4, which indicated that all tested compounds could be classified as preferential COX-2 inhibitors. It can be concluded that 6-gingerol, 6-shogaol, and 6-paradol could be developed as COX-2 inhibitors.

Research paper thumbnail of Molecular modeling study of andrographolide, neoandrographolide, thymoquinone, thymoquinole, aurine tricarboxylic acid, and gallic acid, inhibitors of NF-kappaB

Abstract: NF-kappaB plays a central role in coordinating the expression of various soluble proinf... more Abstract: NF-kappaB plays a central role in coordinating the expression of various soluble proinflammatory mediators, such as cytokines and chemokines. In physiological conditions, NF-kappaB occurs within the cytoplasm and is retained by IkappaB, a protein inhibitor that masks the nuclear localization signal present in the NF-kappaB sequence.

Research paper thumbnail of Photometric Titration Method to Determine Bromination of Red and Yellow Dyes in Crackers

International Journal of Chemistry

In this work, we determined red and yellow dyes in unregistered crackers sold at Jatinangor, West... more In this work, we determined red and yellow dyes in unregistered crackers sold at Jatinangor, West Java, Indonesia, by using photometric titration method based on the bromination reaction of the dyes. The dyes were extracted using a mixture of 2 % of ammonia in 70 % ethanol continued by preparative thin layer chromatography on GF254 silica gel plate, then they were separated and analyzed by using FTIR-8400 Shimadzu infrared spectrophotometer. Bromination reaction was measured by using photometric titration method. Thin layer chromatograms showed that the dyes were not either rhodamine B or tartrazine (Rf of the red and yellow dyes were 0.714 and 0.652, respectively, while those of rhodamine B and tartrazine were 0.591 and 0.673). Infrared spectroscopy showed characteristic peaks of the red dye at 3390.6 cm -1

Research paper thumbnail of Generating a 3D structure model of Histamine-4 receptor for Antiinflammatory Drug Design

involved in allergic pathogenesis, autoimmune diseases such as arthritis, type-I allergic disease... more involved in allergic pathogenesis, autoimmune diseases such as arthritis, type-I allergic diseases such as asthma, conjunctivitis, and rhinitis. This macromolecule has never been crystallized yet. In drug design, the need to obtain 3D structure of macromolecules is to bridge the gap of ligand-and receptorbased methods. Three-dimensional structure of the target is essential for defining the active site and also for designing, improving, and docking of small ligands to the complex target protein. This study was aimed to generate H4R 3D structure that fulfilled the quality parameters of DOPE and QMEAN by using homology modeling principles. The method used in this work was performed in several steps as follows: (1) searching for the H4R sequence data and identifying protein structures similar to the data to be used as templates for H4R; (2) automatic sequence alignment to calculate the similarity between the templates and H4R sequence; (3) building the H4R 3D structure models using SWISS-MODEL and MODELLER 9v7; and (4) validating the 3D structure models by using DOPE, QMEAN, and Ramachandran plot. This study produced four H4R models that were validated by Ramachandran plot. The best model was applied to dock histamine by using AutoDock 4.0.It could be concluded from this work that 3D structure of H4R was able to be generated and applied to dock histamine in its predicted active site. The active site consists of six amino acid residues which are Asp94, Tyr95, Glu182, Trp316, Tyr319, and Phe344. Its agonist, histamine, is bound in the binding site of this protein via the formation of two hydrogen bonds with Asp94 and Tyr319.

Research paper thumbnail of Cytotoxicity of fevicordin-A from Phaleria macrocarpa (Scheff.) Boerl on P 388, HeLa, CasKi, TE-2, TE-8 and Prepuce’s Fibroblast cells

Cancer is a disease caused by abnormal regulation of cells, particularly the mechanism of cell gr... more Cancer is a disease caused by abnormal regulation of cells, particularly the mechanism of cell growth and differentiation. Cancer has high morbidity and mortality. The limitation of medical treatment leads to the findings of an alternative therapy using medicinal plants. Phaleria macrocarpa (Boerl.) Scheff family Thymelaeceae, is a plant which grows in tropical area, mainly in Papua island, Indonesia, and has been used empirically to treat various health problems, amongst which are cancer, diabetes mellitus, and hypertension. Fevicordin A, is a bioactive compound of P. macrocarpa (Boerl.) Scheff. Previous work of Kurnia and his colleagues concluded that this compound has been successfully isolated from the plant and exhibited toxicity on brine shrimp larvas. The objective of this research was to investigate the cytotoxicity of fevicordin A on P388, HeLa, CasKi, TE-2 and TE-8 cancer cells, while its effect on normal cells was performed on fibroblast cells isolated from human prepuce skin. The method used was MTT assay by using 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide reagent. The results of the work indicated that IC 50 values of fevicordin-A on the growth of the cancer cells were 0.01 µg/mL (P388), 1.16 µg/mL (HeLa), 12 µg/mL (CasKi), 40 µg/mL (TE-2), and 14.6 µg/mL (TE-8), whereas the IC 50 on the growth of fibroblast cells was 24.51 µg/mL. These results suggest that fevicordin A may have potential as a cytotoxic agent against leukemia and cervix cancer.

Research paper thumbnail of The determination of quercetin in Plectranthus  scutellarioides (L.) R.Br. leaves extract and its  In Silico Study on Histamine H4 Receptor

Plectranthus scutellarioides (L.) R.Br., or jawer kotok, Family Lamiaceae, grows widely in Indone... more Plectranthus scutellarioides (L.) R.Br., or jawer kotok, Family Lamiaceae, grows widely in Indonesia, and has a long history of therapeutic usage in Indonesian traditional jamu to cure various diseases. The brownish purple leaves of Plecranthus contain alkaloids, saponin, flavonoids, tannin, volatile oils, and quercetin which has been proven to exert antiinflammatory activity. In this research, a determination of quercetin in Plecranthus leaves extract was performed and followed by a study of its interaction with histamine H4 receptor to understand its anti-inflammatory activity. The dry leaves were macerated by using a mixture of methanol and water (1:1) for 48 hours and the solvent was evaporated at low temperature (40-50 o C). Analysis of quercetin in the extract was performed by using reversed-phase HPLC method LC-10AT VP (Shimadzu), Atlantis Hilicsilica C18 (Waters ® ) 150 mm x 4.6 mm, 5 µm as stationary phase and a mixture of acetonitrile, phosphoric acid, and methanol (40:50:10), flow rate 0.8 mL/minute. In silico study of quercetin with histamine H4 receptor was performed by using AutoDock Tools 3.0.5. Histamine H4 receptor (H4R) belongs to G protein-coupled receptors which is involved in arthritis, asthma, and inflammations. The 3D structure model of H4R was built by using MODELLER 9v7. Quercetin contained in Plecranthus leaves extract was 0.05 %. This compound interacted with H4R via hydrogen bond formation with Lys158 (2.006 Å) and Glu182 (2.048 Å), and van der Waals interaction with Trp90, Leu91, Asp94, Tyr95, Phe168, Thr178, Ser179, Tyr319, Phe344, and Tyr340, therefore Plecranthus leaves extract might have a chance to be used as histamine H4 receptor inhibitor.

Research paper thumbnail of Determination of Genistein in the Fermented By-product of Soybean Curd, an Indonesian Food, and Its in vivo Assay on Carrageenan-Induced Mice

Food Science and Engineering

In our country, Indonesia, especially in West Java, people frequently consume fermented by-produc... more In our country, Indonesia, especially in West Java, people frequently consume fermented by-product of soybean curd for their main course. The by-product of curd, usually is discarded, can be fermented using either Neurospora (Neurospora sitophila) or Rhizopus (Rhizopus oligosporus) yeast to make oncom. Genistein is a phytoestrogen, an estrogen-like chemical compound present in plants, that has anti-inflammatory property. Genistein can be determined by UV spectrophotometric method based on the UV absorbance of its complex with aluminum chloride. Addition of acid is a critical point in the procedure. The aim of this research was to know whether genistein is still contained in oncom. This research also studied about oncom's activity on carrageenan-induced mice. Acetosal was used as drug control. Result showed that genistein was detected contained in oncom extract. The in vivo assay indicated that oncom extract (dose 1,000 mg/kg of body weight) reduced oedema in carragenan-induced paw of mice, which potencies were 0.66 times lower than that of acetosal's. Oncom might be useful as food and as a weak inflammation reducer as well.

Research paper thumbnail of Indirect Iodination on the Vinyl Double Bond of Andrographolide

International Journal of Chemistry, Jan 1, 2011

Andrographolide is a bicyclic diterpenoid constituent of Andrographis paniculata which is used ex... more Andrographolide is a bicyclic diterpenoid constituent of Andrographis paniculata which is used extensively in the traditional medicine in Indonesia to treat inflammations. The structure of andrographolide contains an α-alkylidene γ-butyrolactone moiety, two olefin bonds at C-8(C-17) and C-12(C-13), and three hydroxyls at C-3, C-19 and C-14. Andrographolide's structure lacks of aromatic ring, hence the iodination reaction of this compound is quite an interesting challenge to be investigated. Iodine atom was incorporated at vinyl position by indirect reaction. The reaction was divided into two steps, which was started by a bromination in non polar medium, then followed by iodination. It is shown that the principal reaction is the addition of bromine atom to an sp 2 carbon atom of the vinyl group via electrophilic substitution. Bromination was carried out in chloroform solvent at room temperature to produce bromo-andrographolide. The iodination was applied further by using palladium triphenylphosphine catalyst. Positive charge iodine species was produced in situ with the addition of chloramine-T, an oxidizing agent, at 40 ℃. 1 H-NMR study shows that iodine attacked the C-12(C-13) vinyl bond which was confirmed by (1) the disappearance of proton chemical shift of C-12 at δ H 6.86 ppm and (2) the change of proton chemical shifts of C-11 which shifted downfield at δ H 2.74 ppm and 2.63 ppm, due to the deshielding effect of iodine. . (2005). Andrographolide interferes with binding of nuclear factor-kB to DNA in HL-60-derived neutrophilic cells.

Research paper thumbnail of Analyzing the Interaction of Shellegueain A: A Bioactive Compound of Pakis Tangkur (Selliguea feei or Polypodium feei) to Cyclooxygenase Enzyme by Molecular Docking

Asian Journal of Chemistry

Shellegueain A is an active compound contained in pakis tangkur (Selliguea feei or Polypodium fee... more Shellegueain A is an active compound contained in pakis tangkur (Selliguea feei or Polypodium feei). This compound has been proven to show analgesic activity by decreasing writhing response in acetic acid-induced rats. It also showed antiinflammatory activity by significantly reducing oedema in carrageenan-induced rat's paw. The purpose of this study is to examine the binding modes of shellegueain A against COX-1 and COX-2 in terms of hydrogen bonds and docking energy, to understand its analgesic and antiinflammatory properties. The simulation indicated that shellegueain A did not interact with either COX-1 or COX-2 enzymes, while afzelechin (a monomeric metabolite of shellegueain A) did by making hydrogen bonds with Met522.

Research paper thumbnail of The inhibition of andrographolide (Andrographis paniculata) on the expression of carbonic anhydrase in LPS-induced human leucocyte cells

Asian Journal of Plant Sciences

Research paper thumbnail of Radioiodinasi andrografolid dan biodistribusinya dalam mencit untuk perunut inflamasi

Majalah Farmasi Indonesia

Andrografolid adalah senyawa aktif dari Andrographis paniculata (Burm.F) Nees dan merupakan konst... more Andrografolid adalah senyawa aktif dari Andrographis paniculata (Burm.F) Nees dan merupakan konstituen utama yang berbentuk lakton diterpenoid bisiklik. Senyawa ini telah diteliti memiliki aktivitas anti-inflamasi secara in vitro yang terjadi melalui berbagai jalur, yaitu melalui inhibisi ekspresi protein inducible nitric oxide synthase (iNOS), inhibisi produksi radikal oksigen, dan inhibisi aktivasi NF-kappaB. Untuk mengetahui apakah senyawa obat telah menempati targetnya dan di lokasi mana target kerja obat tersebut, diperlukan senyawa tracer (perunut), yaitu senyawa obat yang ditandai dengan radionuklida. Berdasarkan hal tersebut, maka dilakukan penelitian tentang radioiodinasi andrografolid dengan 131 I dan uji biodistribusinya dalam mencit dengan tujuan untuk mengetahui lokasi target kerja andrografolid in vivo. Radioiodinasi dilakukan secara tidak langsung, menggunakan brom cair sebagai leaving group, dilanjutkan dengan iodinasi secara cepat pada suhu 40 o C, menghasilkan andrografolid-131 I dengan rendemen penandaan 72,6 %. Iodinasi terjadi melalui substitusi proton pada C-12. Uji biodistribusi pada mencit yang diinduksi lipopolisakarida memperlihatkan bahwa senyawa ini terdistribusi di semua organ, dan akumulasi tertinggi terjadi di lambung sebesar 16,9%/gram organ. Data ini menunjukkan bahwa induksi dengan lipopolisakarida menyebabkan terjadinya inflamasi di lambung dan menyebabkan terjadi peningkatan produksi prostaglandin, sehingga radioligan andrografolid-131 I terakumulasi di dalam organ tersebut.

Research paper thumbnail of Pemodelan Molekul dalam Kimia Medisinal

This book discusses about the simple basics of molecular modeling which is easily to be understoo... more This book discusses about the simple basics of molecular modeling which is easily to be understood by beginners. It also explains about ligand representation, analysis of binding pocket, interaction of ligand and macromolecule, and the relationship between molecular modeling with in vitro and in vivo studies. Informations concerning molecular modeling freewares are also provided.

Some examples written in this book are based on the author’s experimental results which have been published in journals or presented in seminars.

Research paper thumbnail of Discovering Inhibitors of Tyrosinase Enzyme from Zingiberaceae for Depigmentation Agents

Tyrosinase enzyme, which has two copper ions in its catalytic site, involved in skin pigmentation... more Tyrosinase enzyme, which has two copper ions in its catalytic site, involved in skin pigmentation by catalyzing three oxidation reactions on melanogenesis, that are conversion of L-tirosine to L-DOPA, L-DOPA to dopaquinone, and 5,6-dihydroxyindole to 5,6-indolequinone. An inhibition of melanogenesis was proven in vitro by bioactive compounds of Zingiberaceae plants, which are ethyl p-metoxycinnamate, galangin (IC50 10 μM), 6-gingerol (IC50 25-100 μM), 4-hydroxypanduratin-A (IC50 23.2 μM), isopanduratin-A (IC50 10.6 μM), kaempferol (IC50 0.23 μM), and kaempferida. In this paper we studied the interaction of these compounds with tyrosinase enzyme using AutoDock Vina. The interactions were then compared to arbutin (hydroquinone-β-D-glucoside), kojic acid, and hydroquinone, that have been well known as depigmentation agents in cosmetics. All bioactive compounds of Zingiberaceae plants were able to interact with tyrosinase. Compared to others, kaempferol showed the lowest inhibition constant value (Ki 2.7 µM) and two metal interactions with both copper ions, Cu501 and Cu502, which means that this compound was predicted as the strongest inhibitor of tyrosinase enzyme. Kaempferol interacted with tyrosinase by blocking the entrance of the enzyme’s catalytic site, therefore it will prevent the substrate to react with the enzyme. It can be concluded that bioactive compounds of Zingiberaceae can be developed as an inhibitors of tyrosinase.

Research paper thumbnail of In silico study of andrographolide as protease inhibitors for antimalarial drug discovery

Malaria parasite encodes several homologues of aspartic proteases such as plasmepsin I, II and IV... more Malaria parasite encodes several homologues of aspartic proteases such as plasmepsin I, II and IV which are responsible for degradation of host erythrocyte hemoglobin inside the parasite’s food vacuole, hence plasmepsins are novel targets for antimalarial drug discovery. Previous study concluded that Andrographis paniculata herbs extract has been proven to exert antimalarial activity. The molecular mechanism of this activity was not described. The objective of this paper was to investigate the interaction between andrographolide, a major constituent of Andrographis paniculata with the ligand binding domain of plasmepsin I, II and IV, to find the most favorable binding site as well as to predict the binding mode. Pepstatin, a protease inhibitor, was used as the standard. Docking studies showed that pepstatin gave better binding interactions to plasmepsin I, II and IV with binding affinity and inhibition constant values Ei = -10.3 kcal/mol; Ki = 0.02 uM (plasmepsin I), Ei = -8.9 kcal/mol; Ki = 0.3 uM (plasmepsin II), Ei = -9.3 kcal/mol; Ki = 0.15 uM (plasmepsin IV), respectively while andrographolide showed Ei = -9.8 kcal/mol; Ki = 0.07 uM (plasmepsin I), Ei = -8.7 kcal/mol; Ki = 0.42 uM (plasmepsin II), Ei = -8.8 kcal/mol; Ki = 0.35 uM (plasmepsin IV). According to the result, we concluded that andrographolide could be developed as protease inhibitor for antimalarial drug.

Research paper thumbnail of Computational Study of Triterpenoids of Ganoderma lucidum with Aspartic Protease Enzymes for Discovering HIV-1 and Plasmepsin Inhibitors

Rapid resistance development of HIV-1 and Plasmodium falciparum parasite requires discovery of mo... more Rapid resistance development of HIV-1 and Plasmodium falciparum parasite requires discovery of more potent new drugs. Aspartic protease enzymes expressed by HIV-1 and Plasmodium falciparum could be used as important drug targets. The catalytic site is located at the bottom of a cleft in the enzyme surface and consists of two aspartic acids. Aspartic proteases are inhibited by pepstatin-A, a naturally occurring peptide containing two statins, which replace the amino acids. The hydroxyl group of the statine binds tightly to the catalytically-active aspartic acid residues in the active site of protease, thereby mimicking the transition state of the peptide cleavage. Previous study proved that ganoderiol-F, a triterpenoid isolated from the stem of Ganoderma sinense showed higher affinity towards HIV-1 protease (binding energy= -11.40 kcal/mol and Ki= 4.68 nM) than to plasmepsin I (binding energy= -9.96 kcal/mol and Ki= 50.94 nM). In this paper, computational studies of triterpenoids from Ganoderma lucidum with the catalytic site of HIV-1 protease and plasmepsin I, were performed using AutoDock 4.2. Nelfinavir and KNI-10006 were used as the standards for HIV-1 protease and plasmepsin I, respectively. The four compounds are able to interact with both enzymes. Ganoderat acid-B showed the best affinity to HIV-1 protease (binding energy= -7.49 kcal/mol and Ki= 0.001 mM) which is better than nelfinavir. Furthermore, the best affinity to Plasmepsin I is showed by ganodermanondiol (binding energy= -7.14 kcal/mol and Ki= 0.005 mM which is better than KNI-10006. According to the values of binding energy and inhibition constant, triterpenoids from Ganoderma lucidum could be developed further as both anti-HIV and anti-malaria.

Research paper thumbnail of BIOAVAILABILITY STUDY OF SAMBILOTO (Andrographis paniculata) HERBS INFUSION IN RABBIT

Andrographis paniculata or sambiloto is one of the most widely used medicinal herbs in Indonesia.... more Andrographis paniculata or sambiloto is one of the most widely used medicinal herbs in Indonesia. The main bioactive chemical constituent, andrographolide, has been reported to have various pharmacological activities. Besides its function for medical purposes, the sambiloto herbs infusion is frequently taken to maintain health. This study was conducted to determine the bioavailability of sambiloto herbs infusion in rabbit plasma, stomach, and liver, calculated as total andrographolide. Fourteen male New Zealand white rabbits were used in this study. Sambiloto herbs infusions were administered orally at the dose 7.04mL/kg body weight to each rabbit. Blood samples were taken at intervals 0.0; 0.5; 1.5; 2.0; 3.0; and 5.0h after infusion administration. Sambiloto herbs infusion, which calculated as andrographolide, levels in plasma, stomach, and liver were analyzed by high performance liquid chromatography using C-18 column as stationary phase and a mixture of methanol-double distilled water (60:40) as mobile phase. Bioavailability parameters obtained were Cmax 0.5549µg/mL (in stomach), 0.2136µg/mL (in plasma), 0.0051µg/mL (in liver); while tmax 1h (in stomach), 1.5h (in plasma), 2h (in liver); and AUC 1.7451µg.h/mL (in stomach), 0.434µg.h/mL (in plasma), 0.0038µg.h/mL (in liver). These data showed that in healthy animals, sambiloto herbs infusion was fastly absorbed from the stomach, distributed in the circulation system, and metabolized in the liver, in subsequent process. Sambiloto herbs infusion showed good bioavailability in rabbit.

Research paper thumbnail of Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer

Nonivasive diagnosis of cancer can be provided by molecular imaging using hybrid modality to obta... more Nonivasive diagnosis of cancer can be provided by molecular imaging using hybrid modality to obtain better sensitivity, specificity and depiction localization of the disease. In this study, we developed a new molecular imaging agent, radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab in the form of 147Gd-DOTA-PAMAM G3.0-trastuzumab, that can be both target-specific radiopharmaceutical in SPECT as well as targeted contrast agent in MRI for the purpose of diagnosis of HER-2 positive breast cancer. 147Gd radionuclide emits γ-rays that can be used in SPECT modality, but because of technical constraint, 147Gd radionuclide was simulated by its radioisotope, 153Gd. Gd-DOTA complex has also been known as good MRI contrast agent. PAMAM G3.0 is useful to concentrate Gd-DOTA compelexes in large quantities, thus minimizing the number of trastuzumab molecules used. Trastuzumab is human monoclonal antibody that can spesifically interact with HER-2. Synthesis of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab was initiated by conjugating DOTA NHS ester ligand with PAMAM G3.0 dendrimer. The DOTA-PAMAM G3.0 produced was conjugated to trastuzumab molecule and labeled with 153Gd. Characterization DOTA-PAMAM G3.0-trastuzumab immunoconjugate was performed using HPLC system equipped with SEC. The formation of immunoconjugate was indicated by the shorter retention time (6.82 min) compared to that of trastuzumab (7.06 min). Radiochemical purity of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab was >99% after purification process by PD-10 desalting column. Radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab compound was stable at room temperature and at 2–8 0C as indicated by its radiochemical purity 97.6 ± 0.5%–99.1 ± 0.5% after 144 h storage.

Research paper thumbnail of Determination of Safrole in Ethanol Extract of Nutmeg (Myristica fragrans Houtt) using RP-HPLC

Dehydrodiisoeugenol (DDIE), myristicin, and safrole are chemical compounds contained in fruit and... more Dehydrodiisoeugenol (DDIE), myristicin, and safrole are chemical compounds contained in fruit and seed of nutmeg (Myristica fragrans Houtt). DDIE shows antidiabetic activity on PPARγ receptor, while myristicin is hallucinogenic agent. Of the three compounds, safrole is the most toxic substance due to its carcinogenic activity. In this work, we developed an analytical method to determine safrole in ethanol extract of nutmeg. Reversed-Phase High Performance Liquid Chromatography (Dionex Ultimate 3000) using C-18 LiChroCART 250-4, LiChrospher 100 RP 18e (5 µm) 250 mm column as stationary phase, was selected as the method of analysis. A mixture of methanol:water (73:27) at flow rate 1 mL/min was used as mobile phase. Detection was done at 282 nm. Using such conditions, retention time for safrole was 10.45 minutes. The recovery was 101.421%, while the value of CV was 0.838%. LOD and LOQ were 0.668 µg/mL and 2.023 µg/mL, respectively. Mean concentration of safrole in the nutmeg seed extract was 10.979%.

Research paper thumbnail of Molecular Modeling Study of PPAR-gamma Agonists: Dehydro-Di-Isoeugenol, Macelignan, Pioglitazon, Netoglitazon, Rosiglitazon as Antidiabetic Drugs

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated trasncription factor... more The peroxisome proliferator-activated receptors (PPARs) are ligand-activated trasncription factors belonging to the nuclear receptor family. The objective of this study is to analyze the molecular aspects of PPARγ agonists which used to design of new antidiabetic drugs. The analysis method was comparing the interactions of ligands in the ligand binding domain of the PPARγ. This analysis showed that most known agonists of PPARγ interacted via hydrogen bond with Tyr473. Pioglitazone showed three hydrogen bonds with His323 and Tyr473. Netoglitazone showed four hydrogen bonds with Ser289, His323, His449, and Tyr473. Rosiglitazone showed five hydrogen bonds with Ser289, His323, His449, and Tyr473. AZ72, an agonist of PPARα and γ showed five hydrogen bonds with Ser289, His323, His449, and Tyr473. Molecular modeling was performed by redocking pioglitazone and rosiglitazone using AutoDock Vina. Docking showed that both pioglitazone (Ki 0.22 μM) and rosiglitazone (Ki 0.70 μM) occupied their origin sites and interacted with Tyr473. Docking simulation was also performed between dehydro-di-isoeugenol and macelignan to visualize the interaction with PPARγ. These two compounds are found in nutmeg's seed (Myristica fragrans Hout) that have been proven had antidiabetic activity in vitro. It can be concluded that agonists of PPARγ should have hydrogen bond donor and acceptor groups for interacting with Tyr473. Tyr473 might be a critical site of interaction between the PPARγ ligand binding domain and its agonists.

Research paper thumbnail of INTERACTIONS OF GANODERIOL-F WITH ASPARTIC PROTEASES OF HIV AND PLASMEPSIN  FOR ANTI-HIV AND ANTI-MALARIA DISCOVERY

International Journal of Pharmacy and Pharmaceutical Sciences, Jun 3, 2014

Objective: HIV-1 has been a killer disease since two decades ago, while a potential cure has not ... more Objective: HIV-1 has been a killer disease since two decades ago, while a potential cure has not yet discovered due to the fast mutations of the HIV-1 enzymes,i.e reverse transcriptase, integrase, and protease. Apart of HIV-1, malaria has been the biggest cause of death in human and it is mostly found in the East part of Indonesia. There are some enzymes in the food vacuole of Plasmodium falciparum which are the targets of anti-malaria discovery, e.g. plasmepsin I, II, IV, and histo-aspartic protease (HAP). Both plasmepsin and HIV-1 protease are aspartic proteases, therefore a single drug could be designed to inhibit both enzymes. Ganoderiol-F is a triterpenoid isolated from the stem of Ganodermasinensewhich shows inhibition on HIV-1 protease with IC50 20-40 μM.

Research paper thumbnail of Structure-based in silico study of 6-gingerol, 6-shogaol, and 6-paradol, active compounds of  ginger (Zingiber officinale) as COX-2 inhibitors

International Journal of Chemistry, Jun 6, 2013

Ginger's (Zingiber officinale) phenolic compounds, that are 6-gingerol, 6-shogaol, and 6-paradol,... more Ginger's (Zingiber officinale) phenolic compounds, that are 6-gingerol, 6-shogaol, and 6-paradol, have been proven to show anti-inflammatory activity. The purpose of this paper was to discover whether these compounds are potential to be used as COX-2 inhibitors through structure-based in silico study, which is based on the character of the receptor. Docking was performed to the binding pockets of both COX-1 and COX-2 enzymes, to examine their selective character on COX-2. The binding pockets used in this project were the sites where flurbiprofen and SC-58, crystallized in the enzymes. The scoring value of the interaction of 6-gingerol, 6-shogaol, and 6-paradol with COX-1 were -7.40, -7.27, and -7.20 kcal/mol, while with COX-2 were -7.97, -8.10, and -7.80 kcal/mol, respectively. K i value to COX-1 were 3.78, 4.66, and 5.30 μM, while to COX-2 were 1.46, 1.16, and 1.93 μM, respectively. We also calculated the selectivity index value of these compounds to COX-2 and resulted an interval of 0.2 to 0.4, which indicated that all tested compounds could be classified as preferential COX-2 inhibitors. It can be concluded that 6-gingerol, 6-shogaol, and 6-paradol could be developed as COX-2 inhibitors.

Research paper thumbnail of Molecular modeling study of andrographolide, neoandrographolide, thymoquinone, thymoquinole, aurine tricarboxylic acid, and gallic acid, inhibitors of NF-kappaB

Abstract: NF-kappaB plays a central role in coordinating the expression of various soluble proinf... more Abstract: NF-kappaB plays a central role in coordinating the expression of various soluble proinflammatory mediators, such as cytokines and chemokines. In physiological conditions, NF-kappaB occurs within the cytoplasm and is retained by IkappaB, a protein inhibitor that masks the nuclear localization signal present in the NF-kappaB sequence.

Research paper thumbnail of Photometric Titration Method to Determine Bromination of Red and Yellow Dyes in Crackers

International Journal of Chemistry

In this work, we determined red and yellow dyes in unregistered crackers sold at Jatinangor, West... more In this work, we determined red and yellow dyes in unregistered crackers sold at Jatinangor, West Java, Indonesia, by using photometric titration method based on the bromination reaction of the dyes. The dyes were extracted using a mixture of 2 % of ammonia in 70 % ethanol continued by preparative thin layer chromatography on GF254 silica gel plate, then they were separated and analyzed by using FTIR-8400 Shimadzu infrared spectrophotometer. Bromination reaction was measured by using photometric titration method. Thin layer chromatograms showed that the dyes were not either rhodamine B or tartrazine (Rf of the red and yellow dyes were 0.714 and 0.652, respectively, while those of rhodamine B and tartrazine were 0.591 and 0.673). Infrared spectroscopy showed characteristic peaks of the red dye at 3390.6 cm -1

Research paper thumbnail of Generating a 3D structure model of Histamine-4 receptor for Antiinflammatory Drug Design

involved in allergic pathogenesis, autoimmune diseases such as arthritis, type-I allergic disease... more involved in allergic pathogenesis, autoimmune diseases such as arthritis, type-I allergic diseases such as asthma, conjunctivitis, and rhinitis. This macromolecule has never been crystallized yet. In drug design, the need to obtain 3D structure of macromolecules is to bridge the gap of ligand-and receptorbased methods. Three-dimensional structure of the target is essential for defining the active site and also for designing, improving, and docking of small ligands to the complex target protein. This study was aimed to generate H4R 3D structure that fulfilled the quality parameters of DOPE and QMEAN by using homology modeling principles. The method used in this work was performed in several steps as follows: (1) searching for the H4R sequence data and identifying protein structures similar to the data to be used as templates for H4R; (2) automatic sequence alignment to calculate the similarity between the templates and H4R sequence; (3) building the H4R 3D structure models using SWISS-MODEL and MODELLER 9v7; and (4) validating the 3D structure models by using DOPE, QMEAN, and Ramachandran plot. This study produced four H4R models that were validated by Ramachandran plot. The best model was applied to dock histamine by using AutoDock 4.0.It could be concluded from this work that 3D structure of H4R was able to be generated and applied to dock histamine in its predicted active site. The active site consists of six amino acid residues which are Asp94, Tyr95, Glu182, Trp316, Tyr319, and Phe344. Its agonist, histamine, is bound in the binding site of this protein via the formation of two hydrogen bonds with Asp94 and Tyr319.

Research paper thumbnail of Cytotoxicity of fevicordin-A from Phaleria macrocarpa (Scheff.) Boerl on P 388, HeLa, CasKi, TE-2, TE-8 and Prepuce’s Fibroblast cells

Cancer is a disease caused by abnormal regulation of cells, particularly the mechanism of cell gr... more Cancer is a disease caused by abnormal regulation of cells, particularly the mechanism of cell growth and differentiation. Cancer has high morbidity and mortality. The limitation of medical treatment leads to the findings of an alternative therapy using medicinal plants. Phaleria macrocarpa (Boerl.) Scheff family Thymelaeceae, is a plant which grows in tropical area, mainly in Papua island, Indonesia, and has been used empirically to treat various health problems, amongst which are cancer, diabetes mellitus, and hypertension. Fevicordin A, is a bioactive compound of P. macrocarpa (Boerl.) Scheff. Previous work of Kurnia and his colleagues concluded that this compound has been successfully isolated from the plant and exhibited toxicity on brine shrimp larvas. The objective of this research was to investigate the cytotoxicity of fevicordin A on P388, HeLa, CasKi, TE-2 and TE-8 cancer cells, while its effect on normal cells was performed on fibroblast cells isolated from human prepuce skin. The method used was MTT assay by using 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide reagent. The results of the work indicated that IC 50 values of fevicordin-A on the growth of the cancer cells were 0.01 µg/mL (P388), 1.16 µg/mL (HeLa), 12 µg/mL (CasKi), 40 µg/mL (TE-2), and 14.6 µg/mL (TE-8), whereas the IC 50 on the growth of fibroblast cells was 24.51 µg/mL. These results suggest that fevicordin A may have potential as a cytotoxic agent against leukemia and cervix cancer.

Research paper thumbnail of The determination of quercetin in Plectranthus  scutellarioides (L.) R.Br. leaves extract and its  In Silico Study on Histamine H4 Receptor

Plectranthus scutellarioides (L.) R.Br., or jawer kotok, Family Lamiaceae, grows widely in Indone... more Plectranthus scutellarioides (L.) R.Br., or jawer kotok, Family Lamiaceae, grows widely in Indonesia, and has a long history of therapeutic usage in Indonesian traditional jamu to cure various diseases. The brownish purple leaves of Plecranthus contain alkaloids, saponin, flavonoids, tannin, volatile oils, and quercetin which has been proven to exert antiinflammatory activity. In this research, a determination of quercetin in Plecranthus leaves extract was performed and followed by a study of its interaction with histamine H4 receptor to understand its anti-inflammatory activity. The dry leaves were macerated by using a mixture of methanol and water (1:1) for 48 hours and the solvent was evaporated at low temperature (40-50 o C). Analysis of quercetin in the extract was performed by using reversed-phase HPLC method LC-10AT VP (Shimadzu), Atlantis Hilicsilica C18 (Waters ® ) 150 mm x 4.6 mm, 5 µm as stationary phase and a mixture of acetonitrile, phosphoric acid, and methanol (40:50:10), flow rate 0.8 mL/minute. In silico study of quercetin with histamine H4 receptor was performed by using AutoDock Tools 3.0.5. Histamine H4 receptor (H4R) belongs to G protein-coupled receptors which is involved in arthritis, asthma, and inflammations. The 3D structure model of H4R was built by using MODELLER 9v7. Quercetin contained in Plecranthus leaves extract was 0.05 %. This compound interacted with H4R via hydrogen bond formation with Lys158 (2.006 Å) and Glu182 (2.048 Å), and van der Waals interaction with Trp90, Leu91, Asp94, Tyr95, Phe168, Thr178, Ser179, Tyr319, Phe344, and Tyr340, therefore Plecranthus leaves extract might have a chance to be used as histamine H4 receptor inhibitor.

Research paper thumbnail of Determination of Genistein in the Fermented By-product of Soybean Curd, an Indonesian Food, and Its in vivo Assay on Carrageenan-Induced Mice

Food Science and Engineering

In our country, Indonesia, especially in West Java, people frequently consume fermented by-produc... more In our country, Indonesia, especially in West Java, people frequently consume fermented by-product of soybean curd for their main course. The by-product of curd, usually is discarded, can be fermented using either Neurospora (Neurospora sitophila) or Rhizopus (Rhizopus oligosporus) yeast to make oncom. Genistein is a phytoestrogen, an estrogen-like chemical compound present in plants, that has anti-inflammatory property. Genistein can be determined by UV spectrophotometric method based on the UV absorbance of its complex with aluminum chloride. Addition of acid is a critical point in the procedure. The aim of this research was to know whether genistein is still contained in oncom. This research also studied about oncom's activity on carrageenan-induced mice. Acetosal was used as drug control. Result showed that genistein was detected contained in oncom extract. The in vivo assay indicated that oncom extract (dose 1,000 mg/kg of body weight) reduced oedema in carragenan-induced paw of mice, which potencies were 0.66 times lower than that of acetosal's. Oncom might be useful as food and as a weak inflammation reducer as well.

Research paper thumbnail of Indirect Iodination on the Vinyl Double Bond of Andrographolide

International Journal of Chemistry, Jan 1, 2011

Andrographolide is a bicyclic diterpenoid constituent of Andrographis paniculata which is used ex... more Andrographolide is a bicyclic diterpenoid constituent of Andrographis paniculata which is used extensively in the traditional medicine in Indonesia to treat inflammations. The structure of andrographolide contains an α-alkylidene γ-butyrolactone moiety, two olefin bonds at C-8(C-17) and C-12(C-13), and three hydroxyls at C-3, C-19 and C-14. Andrographolide's structure lacks of aromatic ring, hence the iodination reaction of this compound is quite an interesting challenge to be investigated. Iodine atom was incorporated at vinyl position by indirect reaction. The reaction was divided into two steps, which was started by a bromination in non polar medium, then followed by iodination. It is shown that the principal reaction is the addition of bromine atom to an sp 2 carbon atom of the vinyl group via electrophilic substitution. Bromination was carried out in chloroform solvent at room temperature to produce bromo-andrographolide. The iodination was applied further by using palladium triphenylphosphine catalyst. Positive charge iodine species was produced in situ with the addition of chloramine-T, an oxidizing agent, at 40 ℃. 1 H-NMR study shows that iodine attacked the C-12(C-13) vinyl bond which was confirmed by (1) the disappearance of proton chemical shift of C-12 at δ H 6.86 ppm and (2) the change of proton chemical shifts of C-11 which shifted downfield at δ H 2.74 ppm and 2.63 ppm, due to the deshielding effect of iodine. . (2005). Andrographolide interferes with binding of nuclear factor-kB to DNA in HL-60-derived neutrophilic cells.

Research paper thumbnail of Analyzing the Interaction of Shellegueain A: A Bioactive Compound of Pakis Tangkur (Selliguea feei or Polypodium feei) to Cyclooxygenase Enzyme by Molecular Docking

Asian Journal of Chemistry

Shellegueain A is an active compound contained in pakis tangkur (Selliguea feei or Polypodium fee... more Shellegueain A is an active compound contained in pakis tangkur (Selliguea feei or Polypodium feei). This compound has been proven to show analgesic activity by decreasing writhing response in acetic acid-induced rats. It also showed antiinflammatory activity by significantly reducing oedema in carrageenan-induced rat's paw. The purpose of this study is to examine the binding modes of shellegueain A against COX-1 and COX-2 in terms of hydrogen bonds and docking energy, to understand its analgesic and antiinflammatory properties. The simulation indicated that shellegueain A did not interact with either COX-1 or COX-2 enzymes, while afzelechin (a monomeric metabolite of shellegueain A) did by making hydrogen bonds with Met522.

Research paper thumbnail of The inhibition of andrographolide (Andrographis paniculata) on the expression of carbonic anhydrase in LPS-induced human leucocyte cells

Asian Journal of Plant Sciences

Research paper thumbnail of Radioiodinasi andrografolid dan biodistribusinya dalam mencit untuk perunut inflamasi

Majalah Farmasi Indonesia

Andrografolid adalah senyawa aktif dari Andrographis paniculata (Burm.F) Nees dan merupakan konst... more Andrografolid adalah senyawa aktif dari Andrographis paniculata (Burm.F) Nees dan merupakan konstituen utama yang berbentuk lakton diterpenoid bisiklik. Senyawa ini telah diteliti memiliki aktivitas anti-inflamasi secara in vitro yang terjadi melalui berbagai jalur, yaitu melalui inhibisi ekspresi protein inducible nitric oxide synthase (iNOS), inhibisi produksi radikal oksigen, dan inhibisi aktivasi NF-kappaB. Untuk mengetahui apakah senyawa obat telah menempati targetnya dan di lokasi mana target kerja obat tersebut, diperlukan senyawa tracer (perunut), yaitu senyawa obat yang ditandai dengan radionuklida. Berdasarkan hal tersebut, maka dilakukan penelitian tentang radioiodinasi andrografolid dengan 131 I dan uji biodistribusinya dalam mencit dengan tujuan untuk mengetahui lokasi target kerja andrografolid in vivo. Radioiodinasi dilakukan secara tidak langsung, menggunakan brom cair sebagai leaving group, dilanjutkan dengan iodinasi secara cepat pada suhu 40 o C, menghasilkan andrografolid-131 I dengan rendemen penandaan 72,6 %. Iodinasi terjadi melalui substitusi proton pada C-12. Uji biodistribusi pada mencit yang diinduksi lipopolisakarida memperlihatkan bahwa senyawa ini terdistribusi di semua organ, dan akumulasi tertinggi terjadi di lambung sebesar 16,9%/gram organ. Data ini menunjukkan bahwa induksi dengan lipopolisakarida menyebabkan terjadinya inflamasi di lambung dan menyebabkan terjadi peningkatan produksi prostaglandin, sehingga radioligan andrografolid-131 I terakumulasi di dalam organ tersebut.

Research paper thumbnail of The Effect of Soaking, Washing and Frying on the Concentration of Formaldehyde in Sange Belah Salty Fish

Bionatura LPPM Universitas Padjadjaran

Formaldehyde in food has developed as public issue in the last two years. Several foods, such as ... more Formaldehyde in food has developed as public issue in the last two years. Several foods, such as salty fish, wet noodles and tofu were laboratorically proven using formaldehyde as preservative. A study on the effect of soaking and frying towards the concentration of formaldehyde in salty fish has been carried out. Sange belah was chosen as the model. The fish was soaked in formaldehyde solution (250 ppm in concentration) for 12 hours then it was washed, fried, and distilled in closed system. Distillate was reacted with Nash Reagent. The yellow color formed was measured spectrophotometrically at λ 415 nm. Result showed that there was a decreasing of formaldehyde concentration in the sample (∆ 63.27% after washing and ∆ 83.03 % after frying).