Molecular docking Research Papers - Academia.edu (original) (raw)

In the current investigation, the selected phytocompounds of Cocculus hirsutus were screened for potent tau aggregation inhibitors for Alzheimer’s disease through in silico molecular docking. Approximately 19 phytocompounds from Cocculus hirsutus were selected and assessed for their drug likeness based on rule-of-five using Swiss ADME. The phytocompounds that passed rule-of-five were subjected to in silico analysis through molecular docking on Cyclin-dependent kinase 5 (CDK5) and Glycogen synthase kinase 3 beta (GSK3B) using Molegro Virtual Docker v6.0. Molecular docking studies. The molecular interaction on CDK5 and GSK3B enzymes indicate their role in the tau protein aggregation inhibitory activity of the phytocompounds. In silico analysis showed that hirsutine and cohirsinine bind effectively at the active site of target proteins with a MolDock score of -115.08 and -107.29 respectively. The MolDock scores, ReRank scores and interaction poses of the phytocompounds were compared with the known inhibitors of CDK5 and GSK3B enzymes. The present research created a new perspective in understanding hirsutine and cohirsinine phytocompounds as effective inhibitors of tau aggregation and further research in vitro and in vivo may confirm their therapeutic potential in Alzheimer’s.

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- Pharmacology, Pharmacy, Molecular docking, In Silico

Glycogen synthase kinase 3 beta (GSK-3 beta), which is a serine/threonine kinase was initially identified because of its key role in the regulation of glycogen synthesis. But it is now well-established that GSK-3 performs critical functions in many cellular processes, such as apoptosis, tumor growth, cell invasion, and metastasis. Many human disorders, including cancer, have been linked to abnormal GSK-3 activity, underlining its therapeutic promise as a cancer target. [29]. There is conflicting evidence on the effect of GSK-3 inhibition on cancer cell development due to multiple methods through which GSK-3 may influence carcinogenesis. It can act as a tumor promoter as well as a tumor suppressor in different types of cancers [14]. However, it is found that combination of GSK-3 beta inhibitors with chemotherapeutic agents can significantly reduce the resistance of various tumor cells towards the chemotherapy. In the last few years, many GSK-3 inhibitors have been developed, and some are currently being tested in clinical trials [16]. Indazoles are nitrogen-based heterocyclic chemicals that posses many types of biological activities and representatives of this class of pharmacological agents are widely used as antibacterial, anti-inflammatory, anti-HIV, Antiprotozoal and antimalarial agents. Recent studies are showing promising activity of indazole derivatives as anticancer agents.

- by Anu jayamol mathew and +1
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- Medicinal Chemistry, Drug Design, Molecular docking

Consumption of Cassia occidentalis (CO) seeds has been associated with the hepatomyoencephalopathy (HME) in children. Recently, we have characterized the toxic anthraquinones (AQs) such as Emodin, Rhein, Aloe-emodin, Chrysophanol and Physcion in CO seeds and detected these moieties in the bio fluids of CO poisoning cases. As AQs were detected in the serum of HME patients, their interaction with key biomolecules including protein, DNA and glutathione (GSH) is imperative. In this regard, we have previously reported the interaction of these AQs with serum albumin protein and their subsequent biological effects. However, the interaction of these AQs with DNA and GSH remained unexplored. In the present work, we have studied the binding of these AQs of CO seeds with DNA and GSH by fluorescence spectroscopy, UV–vis spectral analysis, molecular docking, and biochemical studies. Results indicated a higher binding affinity for Emodin (K a = 3.854 × 10 4 L mol −1 S −1), Aloe-emodin (K a = 0.961 × 10 4 L mol −1 S −1) and Rhein (K a = 0.034 × 10 4 L mol −1 S −1) towards calf thymus DNA may be associated with their higher cytotoxicity. Alternatively, Physcion and Chrysophanol which showed less cyto-toxicity in our earlier studies exhibited very low DNA binding. The binding pattern of all these AQs is consistent with the in-silico data. Absorption spectroscopy studies indicated the possible formation of GSH conjugate with Aloe-emodin and Physcion. Further biochemical measurement of GSH and GSSG (Glutathione disulfide) following incubation with AQs indicated that Aloe-emodin (28%) and Rhein (30%) oxidizes GSH to GSSG more as compared to other AQs. Taken together, these results suggest that the higher cytotoxicity of Rhein, Emodin and Aloe-emodin may be attributed to their potent DNA and GSH binding affinity.

- by Neeraj Verma and +1
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- Cytotoxicity, Glutathione, Molecular docking, Anthraquinones
- by Karel Berka
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- Organic Chemistry, Cancer, Humans, Molecular docking
- by Diogo Lucio
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- Chemistry, Organic Chemistry, Modeling, Comparative Study

BACKGROUND Colorectal cancer (CRC) or bowel cancer is one of the most important cancer diseases, needing serious attention. The cell surface receptor gene human epidermal growth factor receptor (EGFR) may have an important role in provoking CRC. In this pharmaceutical era, it is always attempted to identify plant-based drugs for cancer, which will have less side effects for human body, unlike the chemically synthesized marketed drugs having serious side effects. So, in this study the authors tried to assess the activity of two important plant compounds, ferulic acid (FA) and p-coumaric acid (pCA), on CRC. MATERIALS AND METHODS FA and pCA were tested for their cytotoxic effects on the human CRC cell line HCT 15 and also checked for the level of gene expression of EGFR by real time PCR analysis. Positive results were confirmed by in silico molecular docking studies using Discovery Studio (DS) 4.0. The drug parallel features of the same compounds were also assessed in silico. RESULTS C...

- by Deepu Mathew
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- Chemistry, Medicine, Gene expression, Colorectal cancer
- by Farukh Arjmand
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- Organic Chemistry, Macromolecular X-Ray Crystallography, DNA, Humans
- by shikhar gupta
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- Obesity, Complementary and Alternative Medicine, Plant Biology, Enzyme Inhibitors
- by Klaus-robert Müller
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- Organic Chemistry, Nuclear Receptor, Humans, Computer Simulation
- by Roberto Maggi
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- Computational Biology, STEROIDS, Molecular Dynamics, Homology Modeling
- by Haim Wolfson
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- Algorithms, Computational Biology, Linear Programming, Enzyme Inhibitors

Fusarium disease causes considerable losses in the cultivation of Piper nigrum, the black pepper used in the culinary world. Brazil was the largest producer of black pepper, but in recent years has lost this hegemony, with a significant reduction in its production, due to the ravages produced by the Fusarium solani f. sp. piperis, the fungus which causes this disease. Scientific research seeks new alternatives for the control and the existence of other Piper species in the Brazilian Amazon, resistant to disease, are being considered in this context. The main constituents of the oil of Piper divaricatum are methyleugenol (75.0%) and eugenol (10.0%). The oil and these two main constituents were tested individually at concentrations of 0.25 to 2.5 mg/mL against F. solani f. sp. piperis, exhibiting strong antifungal index, from 18.0% to 100.0%. The 3D structure of the β-glucosidase from Fusarium solani f. sp. piperis, obtained by homology modeling, was used for molecular docking and mol...

- by Jose Antonio Maia
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- Organic Chemistry, Brazil, Glucose, Fusarium
- by Joyee Mitra
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- Inorganic Chemistry, Coordination Chemistry, Molecular docking

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were conducted on a series (39 molecules) of peptidyl vinyl sulfone derivatives as potential Plasmodium Falciparum cysteine proteases inhibitors. Two different methods of alignment were employed: (i) a receptor-docked alignment derived from the structure-based docking algorithm GOLD and (ii) a

- by Cátia Teixeira
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- Crystal structure, Computer Simulation, Drug Design, Standard Model
- by Kerim Babaoglu
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- Model, Virtual screening, Molecular docking, ROC Curve

Pharmacological studies from our group [Lima et al. Pharmacol Biochem Behav 92:508, (2009)] revealed that geissospermine (GSP), the major alkaloid of the bark extract of Brazilian Geissospermum vellosii, inhibits acetylcholinesterases (AChEs) in the brains of rats and electric eels (Electrophorus electricus). However, the binding mode (i.e., conformation and orientation) of this indole-indoline alkaloid into the AChE active site is unknown. Therefore, in order to propose a plausible binding mode between GSP and AChE, which might explain the observed experimental inhibitory activity, we performed comparative automatic molecular docking simulations using the AutoDock and Molegro Virtual Docker (MVD) programs. A sample of ten crystal structures of the Pacific electric ray (Torpedo californica) TcAChE, in complex with ten diverse active site ligands, was selected as a robust re-docking validation test, and also for GSP docking. The MVD results indicate a preferential binding mode between GSP and AChE, in which GSP functional groups may perform specific interactions with residues in the enzyme active site, according to the ligand–protein contacts detected by the LPC/CSU server. Four hydrogen bonds were detected between GSP and Tyr121, Ser122, Ser200, and His440, in which the last two residues belong to the catalytic triad (Ser200···His440···Glu327). Hydrophobic and π–π stacking interactions were also detected between GSP and Phe330 and Trp84, respectively; these are involved in substrate stabilization at the active site. This study provides the basis to propose structural changes to the GSP structure, such as molecular simplification and isosteric replacement, in order to aid the design of new potential AChE inhibitors that are relevant to the treatment of Alzheimer’s disease. Figure GSP/1DX6 (Molegro Virtual Docker)

- by Josélia Lima and +2
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- Molecular modeling, Molecular, Crystal structure, Humans

G-quadruplex (G4) DNA structures in telomeres and oncogenic promoter regions are potential targets for cancer therapy, and G4 ligands have been shown to modulate telomerase activity and oncogene transcription. Herein we report the synthesis and G4 thermal stabilisation effects, determined by FRET melting assays, of 20 indolo[3,2-b]quinolines mono-, di-, and trisubstituted with basic side chains. Molecular modelling studies were also performed in an attempt to rationalise the ligands′ binding poses with G4. Overall, the results suggest that ligand binding and G4 DNA thermal stabilisation increase with an N5-methyl or a 7-carboxylate group and propylamine side chains, whereas selectivity between G4 and duplex DNA appears to be modulated by the number and relative position of basic side chains. From all the indoloquinoline derivatives studied, the novel trisubstituted compounds 3 d and 4 d, bearing a 7-(aminoalkyl)carboxylate side chain, stand out as the most promising compounds; they show high G4 thermal stabilisation (ΔTm values between 17 and 8 °C) with an inter-G4 ΔTm trend of Hsp90A>KRas21R≈F21T>c-Kit2, 10-fold selectivity for G4 over duplex DNA, and 100-fold selectivity for the HCT116 cancer cell line (IC50 and IC90: <10 μM) over primary rat hepatocytes. Compounds 3 d and 4 d also decreased protein expression levels of Hsp90 and KRas in HCT116 cancer cells.

- by Daniel J V A dos Santos
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- Molecular Dynamics Simulation, Cancer, Molecular docking, Alkaloids

Because of lack of hygienic conditions of living and contaminated potable water system, the rural and urban slum people of Bangladesh suffer in large numbers from gastrointestinal disorders like diarrhea and dysentery (mostly caused by Vibrio cholerae, rotavirus, Escherichia coli and Shigella). More than a third of the 160 million people of the country earns below the poverty level income, defined as less than US$ 1 per day. Because of poverty, year round occurrences of gastrointestinal disorders cause the rural and urban poor to seek traditional medicinal help. Holarrhena antidysenterica (Linn.) Wall., belonging to the Apocynaceae family and known in English as bitter oleander, has been used for possibly thousands of years in the Indian sub-continent countries (like India and Bangladesh) as an effective plant against diarrhea and dysentery. The present review gives an account of ethnomedicinal uses of the plant and plant parts and attempts to justify the traditional use of the plant against diarrhea and dysentery based on scientific reports of the phytochemical constituents of the plant and reported pharmacological activities, as well as molecular docking studies between three constituents (conessine, holarrhenine, and kurchessine) of the plant and Capsid Protein VP6 of Group A rotavirus. The docking energies of the phytochemicals with Capsid Protein VP6 suggest that they can be effective inhibitors of rotavirus and therefore merit further studies as potential drugs against diarrhea and dysentery.

- by Md. Arif Khan
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- Medicinal Plants, Molecular docking, Gastrointestinal Disorders
- by Dr.Aamer Saeed
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- Organic Chemistry, Kinetics, Enzyme Inhibitors, Molecular docking

Dengue caused by the dengue virus (DENV) is a severe health problem in tropical regions such as Southeast Asia, especially Indonesia. Indonesian have used rhizome as traditional medicine for 1300 years. This study investigated the compounds from Kaempferia galanga, Curcuma longa, Zingiber officinale, Curcuma aeruginosa, Curcuma zanthorrhiza, Alpinia galanga, and Allium sativum as antivirals agents, explicitly targeting the DENV envelope protein to inhibit viral fusion. This study involved 121 bioactive compounds and DENV2's prefusion envelope protein. The virtual screening and molecular docking were done through occupied the Lipinski rule of five checker (http://www.scfbio-iitd.res.in/software/ drugdesign/lipinski.jsp) and AutoDock Vina (https://pyrx.sourceforge.io/) respectively. The top nine compounds with the strongest binding affinity were galangin, kampferide, demetoxy curcumin, bisdemethoxycurcumin, β-selinene, 6-(hydroxymethyl)-1,4,4-trimethylbicyclo[3.1.0]hexan-2-ol, piperine, estra-1,3, 5(10)-trien-17β-ol, and curcumin. These compounds' affinity values were significantly lower, around 45-62%, than chloroquine. Most of them interact with the kl hairpin and hydrophobic pocket formed by residues Val130, Leu135, Phe193, Leu198, and Phe279of critical domains that can interfere with the conformational change and rearrangement of protein dimer in the post-fusion stage. This study suggested that the galangin, demethoxycurcumin, and bisdemethoxycurcumin are considered the most potential compounds to be developed as anti-prefusion E DENV2 low-affinity and intense interaction with those.

- by Arief Hidayatullah
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- Bioinformatics, Dengue Virus, Molecular docking, Natural Bioactive Compounds
- by P. Reddanna
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- Protein Folding, Molecular Mechanics, Potato, Homology Modeling

Novel Corona virus is making its Worldwide propagation in a very fast phase. It is now essential to discover the drugs that are useful in the prevention and management of NCoV-19. Many traditional Herbs and Poly Herbal synergistic formulations are useful in the prophylaxis of various types of Viruses. In Siddha system of medicine, there are various medicines used for antiviral therapies. Nilavembu kudineer is a very remarkable medicine which is already recognized by the Government of Tamilnadu during the eradication program of Dengue and Chikungunya viruses. To prove safety and efficacy of a traditional medicine, Reverse pharmacology method is recognized globally. Reverse pharmacology is confirming the safety and efficacy of a medicine which is already in clinical practice by going back in the steps of pharmacological screening and drug development. The ultimate aim of the Reverse pharmacological research is to find the mechanism of action by a drug against a disease. For Nilavembu kudineer (Mentioned in the Siddha text Siddha Vaithiya Thirattu), clinical documentations and various pre-clinical studies on its safety and efficacy are already done. In this study, we have done the In-silico Molecular Docking Analysis of the Bio-active compounds found in the aqueous extract of Nilavembu kudineer chooranam against the ACE2 enzyme receptor which is the route of entry in the pathogenesis of Novel corona virus. Clinical study needs to be done to confirm the proposed efficacy of the Nilavembu kudineer in the prevention of the Novel Corona Virus.

Breast cancer is the cancerous condition that develops in breast tissues, which could be invasive or non-invasive cancer. Hormonal therapy is general practice to control the estrogen level in Estrogen Receptor – positive (ER+) condition of breast cancer. Phytoestrogens that have been hypothesized to reduce risk of breast cancer and Glycine max (Soya bean) is a primary source of isoflavones, which has structure similar to estrogen receptor molecule. Glycine max intake in the diet has been associated with low risk for developing breast cancer. The aim of the study was to identify anti-cancerous potentials from Glycine max with the help of docking studies and molecular orbital analysis. Insilico docking studies were carried out using computational methods, based on Lamarckian genetic algorithm and PM7. This theoretical analysis could lead to further improvement of potent estrogen receptor antagonists for treatment of cancerous conditions.

- by Margaret Fleck
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- Mathematics, Computer Science, Computer Vision, Computational Geometry
- by Uttam Pal
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- Photochemistry, Fluorescence Resonance Energy Transfer, Humans, Computer Simulation

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT3 and 5-HT1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT3 and 5-HT1A receptors, respectively. L-17 robustly increased c-Fos immunoreactivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT3 and 5-HT1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro- and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs.

- by Andrew Good
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- Forecasting, Drug Discovery, Enzyme Inhibitors, Molecular Recognition

African Swine Fever Virus (ASFV) is a dsDNA virus causative of the African Swine Fever (ASF) in wild and domestic hogs. ASF is characterized by hemorrhagic fever, high mortality, and transmissibility. The binding of the DNA to the pA104R protein mediates viral replication and genome packaging. In the present study, we generated nine (9) reference compounds that exhibited high docking affinities through de novo computeraided drug design (CADD). These compounds were then used as query molecules to find commercially available drug-like compounds using ligand-based virtual screening (VS). We were able to retrieve 900 hit compounds that exhibited the same pharmacophoric activities. Then, these hit compounds were subjected to drug-likeness filtration to identify the most likely to be developed as commercial drugs based on established parameters. We identified sixty-two (62) drug-like molecules. Molecular docking was then performed to determine the top five compounds with the highest binding affinities against the target protein. ADME/T profiling was done on these compounds to assess their pharmacokinetic properties. Compound 8.45 performed best based on our devised scoring system. This paper shall serve as a good reference in the discovery and development of anti-ASFV therapeutics.

- by Kim Rafaelle Reyes
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- Bioinformatics, Computational Chemistry, Virtual screening, Drug Design

Human bocavirus 1 (HBoV1) is a newly identified parvovirus that causes serious respiratory infection among children across the globe. Aim of the present study was to predict immunogenic residues located on the VP2 protein of HBoV1 towards development of epitope based vaccines. Several computational tools were employed to predict epitopes (bothT and B cell restricted) with stringent regulation for the improvement of confidence. After meticulous analysis, the peptide "TTPWTYFNFNQY" was identified as potential candidate for development of preventive vaccine. Of note, the epitope "TTPWTYFNFNQY" was found to be recognized by fifteen different alleles belonging to seven HLA supertypes (A1, A3, A24, A26, B7, B58 and B62). Further, mutational variability analysis pointed that most of the amino acids were well conserved. Docking scores obtained from ClusPro and Autodock Vina for selected epitopes displayed energetically favorable and stable interaction of peptide-HLA-I complexes. The core peptide "LLYQMPFFL" was found to recognize by wide range of HLA class II allele recognition thereby qualified as candidate for therapeutic vaccine. Five distinct linear peptides (withT cell epitope superimposition) belonging to B cells were identified in the VP2 protein. Further attention on the enlisted epitopes may shed light on the path for development of diagnostic, therapeutic and preventive tools against HBoV1 infection. Additionally, the predicted epitopes may help us to address the original antigenic sin phenomena observed during consecutive HBoV2-4 infection.

- by Narayanan Kalyanaraman
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- Bioinformatics, HLA, Molecular docking, Reverse Vaccinology

Phenylhydrazine (PHZ), a potent chemical causes toxicity on various tissues at various levels. Administration of phenylhydrazine mainly causes haematotoxicity which leads to the haemolytic anemia. In mammals PHZ induced anemia increased the iron absorption in spleen, liver and duodenum and finally iron metabolism was altered. Local demand and supply of Fe would increase erythropoeitic activity of the spleen so the size of spleen was increased that create the splenomegaly. PHZ induced anemia activate immune response which triggers phagocytosis in the spleen and liver. Apart from this administration of PHZ interfere the binding of erythropoietin (EPO) with erythropoietin receptors (EPOR) so that JAK-STAT would be affected.PHZ also showed genotoxic effect by creating single strand DNA damage.

Virtual screening (VS) is a powerful technique for identifying hit molecules as starting points for medicinal chemistry. The number of methods and softwares which use the ligand and target-based VS approaches is increasing at a rapid pace. What, however, are the real advantages and disadvantages of the VS technology and how applicable is it to drug discovery projects? This review provides a comprehensive appraisal of several VS approaches currently available. In the first part of this work, an overview of the recent progress and advances in both ligand-based VS (LBVS) and structurebased VS (SBVS) strategies highlighting current problems and limitations will be provided. Special emphasis will be given to in silico chemogenomics approaches which utilize annotated ligand-target as well as protein-ligand interaction databases and which could predict or reveal promiscuous binding and polypharmacology, the knowledge of which would help medicinal chemists to design more potent clinical candidates with fewer side effects. In the second part, recent case studies (all published in the last two years) will be discussed where the VS technology has been applied successfully. A critical analysis of these case studies provides a good platform in order to estimate the applicability of various VS strategies in the new lead identification and optimization.

- by Marcos Hikari Toyama
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- Cancer Prevention, Platelet aggregation, Circular Dichroism, Mice

Novel macrocyclic peptide mimetics have been synthesized by exploiting a three-component reaction and an azide–alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed.

- by Manoj Damale
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- Drug Discovery, Humans, Molecular Modelling, Molecular Diversity

The mannose-binding agglutinin from bulbs of Lycoris aurea (LAA) agglutinates rabbit but not human erythrocytes. The molecular mass of the monomer in SDS/PAGE is 12 kDa while the ap - parent molecular mass in gel filtration is 48 kDa, indicating that LAA is a homotetramer. The full-length cDNA of LAA contains 683 bp with an open reading frame encoding a protomer of 162 amino-acid residues. Hydrophobic Cluster Analysis and molecular modeling of the 109-resi - due mature polypeptide suggested a similar secondary and tertiary structure to those of Narcissus pseudonarcissus agglutinin (NPA). Molecular docking revealed that, besides the three mannose- binding sites common among Amaryllidaceae lectins, LAA also contains a fourth unique man- nose-binding site formed by a tryptophan cluster. The existence of four mannose-binding sites in each monomer of LAA is very unusual and has only been reported for NPA earlier.

- by ah yang kong
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- Biology, Medicine, Molecular modeling, Sequence alignment

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be ...

- by Michail Georgakis
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- Bioinformatics, Genetics, Structural Biology, Structural Bioinformatics

At the beginning of 2020, a new type of Coronavirus (Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)) dismayed the world and led to public health emergencies. This virus has caused a remarkable percentage of morbidity and mortality. Also, the lack of an effective treatment to fight this virus is another concern that should be given attention. Herbal medicines and purified natural products have been reported for their antiviral activity against SARS-CoV-2. In this study, molecular docking of effective compounds in the extracts and essential oils of Zingiber officinale, Glycyrrhiza glabra Sambucus nigra, Panax ginseng Ocimum basilicum, and Origanum vulgare was carried out to investigate their binding to the X-ray structure of the ACE2 binding domain of SARS-CoV-2. The Glide docking program was utilized for molecular docking with standard precision (SP) and extra precision (XP). Finally, 7 compounds-mainly belong to Panax ginseng-showed a higher docking score than some kno...

A novel bridged binuclear Cu(II) complex with mixed ligands, di-μ-(2-aminopyridine(N,N′))-bis[(2,6-pyridinedicarboxylate)aquacopper(II)] tetrahydrate, formulated as [Cu(μ-ap)(dipic)(H2O)]2·4H2O (1) (dipic = 2,6-pyridinedicarboxylate, ap = 2-aminopyridine), has been synthesized and characterized by elemental, spectral (IR and UV–Vis.), thermal analysis, magnetic measurements and single crystal X-ray diffraction analysis. The central Cu(II) ion resides on a centre of symmetry in a distorted square-pyramid coordination environment comprising of two N atoms, one from dipic and one from the ap ring, two carboxylate O atoms from dipic, and one O atom from water. Intermolecular N–H⋯O and O–H⋯O hydrogen bonds and π–π stacking interactions seem to be effective in the stabilization of the crystal structure. The free ligands and the complex were also evaluated for their antimicrobial and radical scavenging activities (DPPH = 1,1-diphenyl-2-picrylhydrazyl hydrate) using in vitro microdilution methods. Antimicrobial screening of the free ligands and their complex showed that the free ligands and the complex possess antifungal activity against Candida sp.

- by Halil Sarı
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- Inorganic Chemistry, Organic Chemistry, Biomedical Engineering, Medicinal Chemistry

Development of new antimicrobial agents is a good solution to overcome drug-resistance problems. In this context, new functionalized thiophene, acrylamide, arylhydrazone, pyrazole and pyridone derivatives bearing sulfisoxazole moiety were designed, synthesized and evaluated for their in vitro antibacterial and antifungal activities. Among the synthesized compounds, thiophene 4d and 6-thioglucosylpyridone 17 displayed significant antibacterial activities against Escherichia coli (MIC, 0.007 μg/mL vs gentamycin 1.95 μg/mL) and Bacillis subtilis (MIC, 0.007 μg/mL vs ampicillin 0.24 μg/mL), respectively. Whereas, the pyrazole 6 showed the highest antifungal activity against Aspergillus fumigates (MIC, 0.03 μg/mL vs amphotericin B 0.12 μg/mL). In general, most of the synthesized compounds exhibited better antimicrobial activities than sulfisoxazole; this might be attributed to the synergistic effect of the sulfonamide and attached heterocyclic moieties as well as the increased lipophilic...

- by Samir Bondock
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- Organic Chemistry, Aspergillus, Escherichia coli, Drug Design

A series of 4-alkylaminoaryl phenyl cyclopropyl methanones (6a–6u and 8a–8c) were synthesized from 4-fluorochalcones (3a and 3b) by cyclopropanation of double bond followed by nucleophilic substitution of F with different amines. The compounds were screened for their antitubercular and antimalarial activities against Mycobacterium tuberculosis H37Rv and Plasmodium falciparum 3D7 strains in vitro respectively. Several compounds (6a, 6d–6h, 6p, 6q and 8a–8c) exhibited good in vitro antitubercular activities with MIC values 3.12–12.5 μg/mL and preferentially inhibited the growth of P. falciparum in vitro (4a, 4c, 6a–6d, 6f, 6s, 8a and 8c) with IC50 as low as 0.080 and 0.035 μg/mL and SI values 4975 and 6948, respectively. Molecular docking studies and in vitro evaluation against FAS-II enzymes using reporter gene assays were carried out to elucidate the mode of action of these molecules. Two compounds 4a and 6g showed significant inhibition at 25 μM concentration of the compound.

- by D Kumar
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- Molecular docking, Andrographolide

Diabetes mellitus adalah salah satu penyakit metabolik kronis yang paling umum, ditandai oleh hiperglikemia kronis, perkembangan patologi mikrovaskuler dan makrovaskular khusus diabetes. Hiperglikemia yang berkepanjangan adalah faktor penyebab utama dari beberapa komplikasi diabetes.U ntuk pengobatan diabetes melitus dapat digunakan obat-obat yang mampu mempengaruhi protein Aldosa Reduktase (ALR2) (Boukarai,dkk., 2017). Enzim Aldosa Reductase (ALR2) adalah enzim yang terdapat di beberapa bagian tubuh dan berfungsi dalam metabolisme glukosa jalur poliol yang bertanggung jawab dalam pembentukan fruktosa dan glukosa. Protein ALR2 dapat berikatan dengan obat diabetes menyebabkan terjadinya peristiwa glukosa pada sel diubah menjadi sorbitol fruktosa. Penelitian ini bertujuan untuk menentukan interaksi antara senyawa turunan flavonoid sebagai agen inhibitor ALR2 untuk komplikasi diabetes. Study HKSA dilakukan untuk menentukan senyawa turunan atau senyawa baru yang akan diujikan. Molecular docking dilakukan menggunakan program AutoDock 4.2 dan protein aldose reductase (PDB ID : 2PDB) sebagai makromolekul. Hasil docking senyawa baru menunjukan semua senyawa dapat berinteraksi dengan sisi aktif enzim aldose reductase. Interaksi terbaik ditunjukkan pada senyawa 2 dan 7 dengan nilai binding energy-5,42 dan-6,35. Interkasi antar molekul ikatan hydrogen dengan residu asam amino yang paling mirip dengan ligan alami adalah seyawa 2 dengan residu asam amino TRP 20, TYR 40, CYS 298, LEU 300, HIS 110, CYS 303 dan senyawa 7 dengan residu asam aminoTYR 48, LEU 300, TRP 20, CYS 303, dan HIS 110.

- by Emil Nur Arifah
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- Medicinal Chemistry, Diabetes, Enzyme Inhibitors, Flavonoids

The new pyrimidine-pyrrole scaffolds (7a-7m) with substituted 1,2,3-traizole moiety were synthesized in good to mild yields and subjected for anti-cancer activity against melanoma and breast cancer cell lines using MTT assay. The compounds 7f and 7m exhibited highest anti-cancer activity against both the tested cell lines in in vitro assay. The molecular docking analysis provided the insights of binding orientation of pyrimidine-pyrrole nucleus of current ligands and their crucial interactions with Cys797 and other residues of the EGFR tyrosine kinase active site. The interactions of triazole and its various substituted groups with EGFR tyrosine kinase have been discussed.

- by Ratnakaram Venkata Nadh
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- Synthesis, Molecular docking, Triazoles, Anti-cancer activity
- by Jan Busa
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- Fortran, Mathematical Sciences, Physical sciences, Molecular docking

GC-MS analysis of the essential oils from aerial parts of Thymus migricus Klokov & Des.-Shost, Thymus fallax Fisch. & Mey. and Thymus pubescens Boiss. & Kotschy ex Celak var. pubescens resulted in the identification of 26, 35 and 53 constituents, respectively. The major components in the essential oil of T. migricus were found to be α-terpineol (30.6%), thymol (20.7%) and α-terpinyl acetate (14.9%) while in the essentiol oil of T. fallax cis-carveol (29.6%) and α-terpineol (10.8%). Carvacrol was a dominant compound with a percentage 66.1% of the essential oil of T. pubescens var. pubescens. The data obtained indicate that the essential oils of Thymus species generally exhibit some bacteriostatic activity. The antioxidant activity of the tested essential oils were found to be slightly lower than butylatedhydroxyanisole (BHA).

- by Zehra küçükbay
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- Enzyme Inhibitors, Antioxidants, GC-MS, Essential oils