Virapong Prachayasitikul - Academia.edu (original) (raw)

Papers by Virapong Prachayasitikul

Medicinal Chemistry Research, 2012

Simplified 1,3-disubstituted urea derivatives (11-24) of phenylethylamines, homoveratylamines, 2-... more Simplified 1,3-disubstituted urea derivatives (11-24) of phenylethylamines, homoveratylamines, 2-pyridylethylamines, 2-picolylamines as well as xylylenediamines were synthesized and investigated for their cytotoxic activities. The results revealed that most analogs displayed cytotoxicity against HepG2 and MOLT-3 cell lines. The bis-thiourea derivatives 23 and 24 exhibited higher inhibitory potency against HepG2 cell than the reference drug, etoposide. 1,1 0 -(1,3-phenylenebis(methylene))bis(3-(4-chlorophenyl)thiourea) 24 was shown to be the most potent cytotoxic compound against MOLT-3 cell line with an IC 50 value of 1.62 lM. QSAR studies suggested that compounds with high ionization potential displayed high cytotoxicity against HuCCA-1 cell line. Furthermore, derivatives with dimethoxyphenyl group had high radial distribution function with a correspondingly high cytotoxicity against A549 cell line. Moreover, analogs 23 and 24 had low values of E HOMO (energy of the highest occupied molecular orbital energy) as well as high cytotoxicity against HepG2 cell line. This study affords an easily accessible approach for the synthesis of promising anticancer agents. The developed QSAR models provided pertinent information into the physicochemical properties governing the investigated biologic properties.

a b s t r a c t 8-Hydroxyquinoline (8HQ) compounds have been reported to possess diverse bioactiv... more a b s t r a c t 8-Hydroxyquinoline (8HQ) compounds have been reported to possess diverse bioactivities. In recent years, drug repositioning has gained considerable attention in drug discovery and development. Herein, 8HQ (1) and its derivatives (2-9) bearing various substituents (amino, nitro, cyano and halogen) were investigated for their antimicrobial against 27 microorganisms (agar dilution method) and antioxidant (DPPH method) activities. The parent 8HQ (1) exerted a highly potent antimicrobial activity against Gram-positive bacteria including diploid fungi and yeast with MIC values in the range of 3.44-13.78 μM. Moreover, the halogenated 8HQ, especially 7-bromo-8HQ (4) and clioquinol , displayed a high antigrowth activity against Gram-negative bacteria compared with the parent compound (1). Apparently, the derivatives with a relatively high safely index, e.g., nitroxoline (2), exhibited strong antibacterial activity against Aeromonas hydrophila (MIC¼5.26 μM) and selectively inhibited the growth of P. aeruginosa with the MIC value of 84.14 μM; cloxyquin (3) showed a strong activity against Listseria monocytogenes and Plesiomonas shigelloides with MIC values of 5.57 and 11.14 μM, respectively. Most compounds displayed an antioxidant activity. Specifically, 5-amino-8HQ (8) was shown to be the most potent antioxidant (IC 50 ¼8.70 μM) compared with the positive control (α-tocopherol) with IC 50 of 13.47 μM. The findings reveal that 8HQ derivatives are potential candidates to be further developed as antimicrobial and antioxidant agents.

Spilanthes acmella, a well known antitoothache plant with high medicinal usages, has been recogni... more Spilanthes acmella, a well known antitoothache plant with high medicinal usages, has been recognized as an important medicinal plant and has an increasingly high demand worldwide. From its traditional uses in health care and food, extensive phytochemical studies have been reported. This review provides an overview and general description of the plant species, bio-active metabolites and important pharmacological activities including the preparation, purification and in vitro large-scale production. Structure-activity relationships of the bioactive compounds have been discussed. Considering data from the literature, it could be demonstrated that S. acmella possesses diverse bioactive properties and immense utilization in medicine, health care, cosmetics and as health supplements. As a health food, it is enriched with high therapeutic value with high potential for further development.

Journal of Microbiological Methods, 2008

Rapid diagnosis for differentiation of leptospirosis from other pyrogenic infections prevailing i... more Rapid diagnosis for differentiation of leptospirosis from other pyrogenic infections prevailing in the same locality is imperative for proper treatment. During infection, the pathogenic Leptospira spp. express virulence factors which induce antibody responses in the infected host. In this study, 50 referenced Leptospira spp. belonging to six genomospecies and 10 L. interrogans clinical isolates were studied for the presence of a gene encoding an in vivo expressed, surface exposed, immunoglobulin-like protein, LigA, by using PCR and southern hybridization specific to the 5′ terminus sequence of the DNA. LigA was also detected in the Leptospira spp. whole cell homogenates by a direct ELISA using a mouse antiserum to the C-terminal portion of recombinant LigA (cLigA) as a detection reagent. All pathogenic Leptospira spp. except one of the two strains of L. santorasai were positive for the gene and its phenotype while all of the L. borgpetersenii and L. biflexa strains were negative. Recombinant cLigA was used as an antigen in ELISAs for detecting IgM and IgG in the sera of leptospirosis patients and in the sera of patients with other febrile illnesses and healthy subjects. When acute phase sera were tested by the cLigA IgM-and IgG-ELISAs, 92% and 100% of the MAT-positive sera were positive, respectively. The diagnostic sensitivity was 100% when both IgM-and IgG-ELISAs were performed on the same acute phase sera and the results were combined. Acute and convalescence sera of patients who were Leptospira culture positive but MAT/IgM-dipstick negative gave 88% and 100% positives by combined cLigA IgM/IgG ELISAs. The diagnostic specificities for the cLigA IgM-and IgG-ELISAs were 98% and 100%, respectively. Our cLigA based-serology has a high potential for early diagnosis of leptospirosis especially when the culture and MAT results are not yet available.

DNA and Cell Biology, 2001

Induction of manganese superoxide dismutase (MnSOD) in response to oxidative stress has been well... more Induction of manganese superoxide dismutase (MnSOD) in response to oxidative stress has been well established in animals, tissues, and cell culture. However, the role of the human MnSOD (hMnSOD) promoter in stimulus-dependent activation of transcription is unknown. The hMnSOD promoter lacks both a TATA and a CAAT box but possesses several GC motifs. In a previous study, we showed that the basal promoter contains multiple Sp1 and AP-2 binding sites and that Sp1 is essential for the constitutive expression of the hMnSOD gene. In this study, we identified an Egr-1 binding site in the basal promoter of hMnSOD. We also found that the basal promoter is responsive to 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated hMnSOD transcription in the human hepatocarcinoma cell line HepG2. The contributions of these binding sites and the roles of the transcription factors Egr-1, AP-2, and Sp1 in the activation of hMnSOD transcription by TPA were investigated by site-directed mutation analysis, Western blotting, and overexpression of transcription factors. The results showed that Sp1 plays a positive role for both basal and TPA-activated hMnSOD transcription, whereas overexpression of Egr-1 has a negative role in the basal promoter activity without any effect on TPA-mediated activation of hMnSOD transcription.

Molecular Diversity, 2015

Hepatitis C virus (HCV) is composed of structural and non-structural proteins involved in viral t... more Hepatitis C virus (HCV) is composed of structural and non-structural proteins involved in viral transcription and propagation. In particular, NS5B is an RNAdependent RNA polymerase for viral transcription and genome replication and is a target for designing antiviral agents. In this study, classification and quantitative structure-activity relationship (QSAR) models of HCV NS5B inhibitors were constructed using the Correlation and Logic software. Molecular descriptors for a set of 970 HCV NS5B inhibitors were encoded using the simplified molecular input line entry system notation, and predictive models were built via the Monte Carlo method. The QSAR models provided acceptable correlation coefficients of R 2 and Q 2 in the ranges of 0.6038-0.7344 and 0.6171-0.7294, respectively, while the classification models displayed sensitivity, specificity, and accuracy in ranges of 88. 24-98.84, 83.87-93.94, and 86.50-94.41 %, respectively. Furthermore, molecular fragments as substructures involved in increased and decreased inhibitory activities were explored. The results

EXCLI Journal

P-glycoprotein (Pgp) is a drug transporter that plays important roles in multidrug resistance and... more P-glycoprotein (Pgp) is a drug transporter that plays important roles in multidrug resistance and drug pharmacokinetics. The inhibition of Pgp has become a notable strategy for combating multidrug-resistant cancers and improving therapeutic outcomes. However, the polyspecific nature of Pgp, together with inconsistent results in experimental assays, renders the determination of endpoints for Pgp-interacting compounds a great challenge. In this study, the classification of a large set of 2,477 Pgp-interacting compounds (i.e., 1341 inhibitors, 913 non-inhibitors, 197 substrates and 26 non-substrates) was performed using several machine learning methods (i.e., decision tree induction, artificial neural network modelling and support vector machine) as a function of their physicochemical properties. The models provided good predictive performance, producing MCC values in the range of 0.739-1 for internal cross-validation and 0.665-1 for external validation. The study provided simple and i...

European Food Research and Technology, 2014

ABSTRACT Abstract Cardiovascular disease is one of the major health problems worldwide. It is a v... more ABSTRACT Abstract Cardiovascular disease is one of the major health problems worldwide. It is a vascular condition known as an atherosclerosis referring to the accumulation of immune cells and lipids in vascular walls that finally obstructs blood flow to trigger heart attack. To prevent and treat the atherosclerosis is to control blood lipid level. Diverse classes of lipid-lowering drug have been used. Nicotinic acid (niacin or vitamin B3) is the first drug that has been used for over five decades. Nicotinic acid and its derivatives play important role as multifunctional pharmacophores exerting a variety of biological activities. This review focuses on the redox and non-redox reactions as well as antioxidant activity of nicotinic acid derivatives and drugs acting on nicotinic acid receptor including therapeutic and cosmetic applications. Structure–activity relationship of nicotinic acid derivatives has been discussed. This article could provide insight into the rational design and development of novel bioactive compounds with therapeutic potential. Graphical Abstract

Drug Design, Development and Therapy, 2013

Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalan... more Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalance is the leading cause for many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. 8-Hydroxyquinoline (8HQ) is a small planar molecule with a lipophilic effect and a metal chelating ability. As a result, 8HQ and its derivatives hold medicinal properties such as antineurodegenerative, anticancer, antioxidant, antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed together with their mechanisms of actions and structure-activity relationships.

Drug Design, Development and Therapy, 2014

Purpose: Estrogens play important roles in the pathogenesis and progression of breast cancer as w... more Purpose: Estrogens play important roles in the pathogenesis and progression of breast cancer as well as estrogen-related diseases. Aromatase is a key enzyme in the rate-limiting step of estrogen production, in which its inhibition is one strategy for controlling estrogen levels to improve prognosis of estrogen-related cancers and diseases. Herein, a series of metal (Mn, Cu, and Ni) complexes of 8-hydroxyquinoline (8HQ) and uracil derivatives (4-9) were investigated for their aromatase inhibitory and cytotoxic activities. Methods: The aromatase inhibition assay was performed according to a Gentest™ kit using CYP19 enzyme, wherein ketoconazole and letrozole were used as reference drugs. The cytotoxicity was tested on normal embryonic lung cells (MRC-5) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Only Cu complexes (6 and 9) exhibited aromatase inhibitory effect with IC 50 0.30 and 1.7 µM, respectively. Cytotoxicity test against MRC-5 cells showed that Mn and Cu complexes (5 and 6), as well as free ligand 8HQ, exhibited activity with IC 50 range 0.74-6.27 µM. Conclusion: Cu complexes (6 and 9) were found to act as a novel class of aromatase inhibitor. Our findings suggest that these 8HQ-Cu-uracil complexes are promising agents that could be potentially developed as a selective anticancer agent for breast cancer and other estrogenrelated diseases.

International journal of biological sciences, 2007

A novel solvent-exposed analyte channel, generated by F165G substitution, on the surface of green... more A novel solvent-exposed analyte channel, generated by F165G substitution, on the surface of green fluorescent protein (designated His(6)GFPuv/F165G) was successfully discovered by the aid of molecular modeling software (PyMOL) in conjunction with site-directed mutagenesis. Regarding the high predictive performance of PyMOL, two pore-containing mutants namely His(6)GFPuv/H148G and His(6)GFPuv/H148G/F165G were also revealed. The pore sizes of F165G, H148G, and the double mutant H148G/F165G were in the order of 4, 4.5 and 5.5 A, respectively. These mutants were subjected to further investigation on the effect of small analytes (e.g. metal ions and hydrogen peroxide) as elucidated by fluorescence quenching experiments. Results revealed that the F165G mutant exhibited the highest metal sensitivity at physiological pH. Meanwhile, the other 2 mutants lacking histidine at position 148 had lower sensitivity against Zn(2+) and Cu(2+) than those of the template protein (His(6)GFPuv). Hence, a ...

Quantitative structure-activity relationship (QSAR) modeling pertains to the construction of pred... more Quantitative structure-activity relationship (QSAR) modeling pertains to the construction of predictive models of biological activities as a function of structural and molecular information of a compound library. The concept of QSAR has typically been used for drug discovery and development and has gained wide applicability for correlating molecular information with not only biological activities but also with other physicochemical properties,

Bisphenol A (BPA), a ubiquitous chemical used in industries, has attracted great attention due to... more Bisphenol A (BPA), a ubiquitous chemical used in industries, has attracted great attention due to its widespread leakage to the environment and foodstuff. This has spurred great interest in the preparation of synthetic polymers capable of selectively sequestering BPA. In this study, theoretical calculation was utilized to confirm the selection of suitable functional monomer capable of strong interaction with BPA.

A data set comprising of the selectivity index of pentachlorophenol-imprinted polymers against 53... more A data set comprising of the selectivity index of pentachlorophenol-imprinted polymers against 53 pentachlorophenol and related compounds was obtained from the excellent work of Baggiani et al. Molecular descriptors of the phenol compounds were calculated with E- DRAGON to obtain a total of 1,666 descriptors spanning 20 categories of molecular properties. Multivariate analysis of the data set was performed using

The molecular mechanism of ethylenediaminetetraacetic acid (EDTA)-induced membrane destabilizatio... more The molecular mechanism of ethylenediaminetetraacetic acid (EDTA)-induced membrane destabilization has been studied using a combination of four biophysical techniques on artificial lipid membranes. Data from Langmuir film balance and epifluorescence microscopy revealed the fluidization and expansion effect of EDTA on phase behavior of monolayers of either 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or mixtures of DPPC and metal-chelating lipids, such as

Molecular imprinting is one of the most efficient methods for preparing synthetic receptors that ... more Molecular imprinting is one of the most efficient methods for preparing synthetic receptors that possess user defined recognition properties. Despite general success of non-covalent imprinting for a large variety of templates, some groups of compounds remain difficult to tackle due to their structural complexity. In this study we investigate preparation of molecularly imprinted polymers that can bind sulfonamide compounds, which represent important drug candidates. Compared to the biological system that utilizes metal coordinated interaction, the imprinted polymer provided pronounced selectivity when hydrogen bond interaction was employed in an organic solvent. Computer simulation of the interaction between the sulfonamide template and functional monomers pointed out that although methacrylic acid had strong interaction energy with the template, it also possessed high non-specific interaction with the solvent molecules of tetrahydrofuran as well as being prone to self-complexation. On the other hand, 1-vinylimidazole was suitable for imprinting sulfonamides as it did not cross-react with the solvent molecules or engage in self-complexation structures.

Nursing & Health Sciences, 2010

Diabetes mellitus is a chronic disease that affects &amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Diabetes mellitus is a chronic disease that affects &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 180 million people worldwide. It is persistent in Thai communities in spite of much effort in prevention and control. This study examined the knowledge capacity of villagers in the Klongmai community of Nakhon Pathom, Thailand, regarding diabetes by way of action research. A health status assessment and a survey of the community were carried out and used as the basis for designing an educational video on diabetes that is accessible regardless of age and educational background. Evaluations of the pre- and poststudy questionnaires were carried out using statistical analysis. The results indicated that the devised educational materials were effective in encouraging the community&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s self-awareness and perception of diabetes at the significance level of 0.05. Most importantly, the participants demonstrated proficiency in adapting the knowledge gained from the workshop to their own lifestyle.

Molecules, 2008

Nicotinic acid (also known as vitamin B3) is a dietary element essential for physiological and an... more Nicotinic acid (also known as vitamin B3) is a dietary element essential for physiological and antihyperlipidemic functions. This study reports the synthesis of novel mixed ligand complexes of copper with nicotinic and other select carboxylic acids (phthalic, salicylic and anthranilic acids). The tested copper complexes exhibited superoxide dismutase (SOD) mimetic activity and antimicrobial activity against Bacillus subtilis ATCC 6633, with a minimum inhibition concentration of 256 µg/mL. Copper complex of nicotinic-phthalic acids (CuNA/Ph) was the most potent with a SOD mimetic activity of IC 50 34.42 µM. The SOD activities were observed to correlate well with the theoretical parameters as calculated using density functional theory (DFT) at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA) value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), were shown to be appropriate for understanding the mechanism of the metal complexes as their calculated energies show good correlation with the SOD activity. Moreover, copper complex with the highest SOD activity were shown to

Molecules, 2009

Molecular imprinting is a technology that facilitates the production of artificial receptors towa... more Molecular imprinting is a technology that facilitates the production of artificial receptors toward compounds of interest. The molecularly imprinted polymers act as artificial antibodies, artificial receptors, or artificial enzymes with the added benefit over their biological counterparts of being highly durable. In this study, we prepared molecularly imprinted polymers for the purpose of binding specifically to tocopherol (vitamin E) and its derivative, tocopherol acetate. Binding of the imprinted polymers to the template was found to be two times greater than that of the control, non-imprinted polymers, when using only 10 mg of polymers. Optimization of the rebinding solvent indicated that ethanol-water at a molar ratio of 6:4 (v/v) was the best solvent system as it enhanced the rebinding performance of the imprinted polymers toward both tocopherol and tocopherol acetate with a binding capacity of approximately 2 mg/g of polymer. Furthermore, imprinted nanospheres against tocopherol was successfully prepared by precipitation polymerization with ethanol-water at a molar ratio of 8:2 (v/v) as the optimal rebinding solvent. Computer simulation was also performed to provide mechanistic insights on the binding mode of template-monomer complexes. Such polymers show high potential for industrial and medical applications, particularly for selective separation of tocopherol and derivatives.