Papers by Veda Prachayasittikul
SpringerPlus, 2015
Background Great attention has been given towards prevention and treatment of cancers with respec... more Background Great attention has been given towards prevention and treatment of cancers with respect to the impact of disease sequelae on long term well-being of individuals (Vos et al. 2012). Cancers have been reported as one of the Global Burden of Diseases (World Health Organization 2008) and are estimated to be one of main causes of death in the coming decades (Mathers and Loncar 2006; Soerjomataram et al. 2012). Therefore, the search for novel anticancer agents has become one of prime interests in drug discovery and development. 1,2,3-Triazoles are nitrogen heterocycles capable of forming hydrogen bonds which improves their solubility and ability to interact with biomolecular targets (Vatmurge et al. 2008). The 1,2,3-triazoles are highly stable to metabolic degradation as compared to
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.
EXCLI Journal
Aromatase inhibition is an effective treatment strategy for breast cancer. Currently, several in ... more Aromatase inhibition is an effective treatment strategy for breast cancer. Currently, several in silico methods have been developed for the prediction of aromatase inhibitors (AIs) using ar-tificial neural network (ANN) or support vector machine (SVM). In spite of this, there are ample opportunities for further improvements by developing a simple and interpretable quan-titative structure-activity relationship (QSAR) method. Herein, an efficient linear method (ELM) is proposed for constructing a highly predictive QSAR model containing a spontane-ous feature importance estimator. Briefly, ELM is a linear-based model with optimal parame-ters derived from genetic algorithm. Results showed that the simple ELM method displayed robust performance with 10-fold cross-validation MCC values of 0.64 and 0.56 for steroidal and non-steroidal AIs, respectively. Comparative analyses with other machine learning me-thods (i.e. ANN, SVM and decision tree) were also performed. A thorough analysis of in...
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...
Drug Design, Development and Therapy, 2015
Drug Design, Development and Therapy Dovepress submit your manuscript | www.dovepress.com Dovepre... more Drug Design, Development and Therapy Dovepress submit your manuscript | www.dovepress.com Dovepress 4515 O r i g i n a l r e s e a r c h open access to scientific and medical research Open access Full Text article http://dx.
Current topics in medicinal chemistry, 2015
Natural products have been an integral part of sustaining civilizations because of their medicina... more Natural products have been an integral part of sustaining civilizations because of their medicinal properties. Past discoveries of bioactive natural products have relied on serendipity, and these compounds serve as inspiration for the generation of analogs with desired physicochemical properties. Bioactive natural products with therapeutic potential are abundantly available in nature and some of them are beyond exploration by conventional methods. The effectiveness of computational approaches as versatile tools for facilitating drug discovery and development has been recognized for decades, without exception, in the case of natural products. In the post-genomic era, scientists are bombarded with data produced by advanced technologies. Thus, rendering these data into knowledge that is interpretable and meaningful becomes an essential issue. In this regard, computational approaches utilize the existing data to generate knowledge that provides valuable understanding for addressing curr...
Current Topics in Medicinal Chemistry, 2015
Inhibition of non-structural protein 5B (NS5B) represents an attractive strategy for the therapeu... more Inhibition of non-structural protein 5B (NS5B) represents an attractive strategy for the therapeutic treatment of hepatitis C virus (HCV). In this study, machine learning classifiers such as artificial neural network (ANN), support vector machine (SVM), random forest (RF) and decision tree (DT) analyses were used to classify 970 compounds based on their physicochemical properties, including quantum chemical descriptors, constitutional descriptors, functional groups and molecular properties. Good predictive performance was obtained from all classifiers, providing accuracies ranging from 82.47-89.61% for external validation set. SVM was noted as the best classifier, indicated by its highest accuracy of 89.61%. The analyses were performed on data sets stratified by structural scaffolds (nucleoside and non-nucleoside) and bioactivities (active and inactive properties). In addition, a molecular fragment analysis was performed to investigate molecular substructures corresponding to biological activities. Furthermore, common substructures and potential functional groups governing the activities of active and inactive inhibitors were noted for the benefit of rational design and high-throughput screening towards potential HCV NS5B inhibitors.
Curcumin is a major constituent of the turmeric plant Curcuma longa, a member of the Zingiberacea... more Curcumin is a major constituent of the turmeric plant Curcuma longa, a member of the Zingiberaceae family, which is cultivated in India, most parts of Southeast Asia, Asia and other parts of the world. Curcumin has been shown to afford a wide range of pharmacological activities encompassing antioxidative, anti-inflammatory, antibacterial, antifungal, antiviral, antiproliferative, proapoptotic and anti-atherosclerotic effects as well as medicinal benefits against neurodegenerative diseases, arthritis, allergy, inflammatory bowel disease, nephrotoxicity, AIDS, psoriasis, diabetes, multiple sclerosis, cardiovascular disease and lung fibrosis. Moreover, curcumin could suppress inflammatory cytokines as well as suppress various target proteins in cancer cell lines. Owing to its multi-faceted health benefits, curcumin has been used as health supplements as well as natural remedy while several clinical trials are under way to investigate its potential therapeutic usage. This chapter discus...
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.
European Journal of Medicinal Chemistry, 2014
A series of 2-substituted amino-3-chloro-1,4-naphthoquinone derivatives (3e12) were synthesized a... more A series of 2-substituted amino-3-chloro-1,4-naphthoquinone derivatives (3e12) were synthesized as anticancer agents and tested against four cancer cell lines including HepG2, HuCCA-1, A549 and MOLT-3. The most potent cytotoxic activity against the HepG2, HuCCA-1 and A549 cell lines was found to be macetylphenylamino-1,4-naphthoquinone (8) affording IC 50 values of 4.758, 2.364 and 12.279 mM, respectively. On the other hand, p-acetylphenylamino-1,4-naphthoquinone (9) exhibited the most potent cytotoxic activity against the MOLT-3 cell line with an IC 50 of 2.118 mM. Quantitative structureeactivity relationship (QSAR) investigations provided good predictive performance as observed from crossvalidated R of 0.9177e0.9753 and RMSE of 0.0614e0.1881. The effects of substituents at the 2-amino position on the naphthoquinone core structure and its corresponding influence on the cytotoxic activity were investigated by virtually constructing additional 1,4-naphthoquinone compounds (13e36) for which cytotoxic activities were predicted using equations obtained from the previously constructed QSAR models. Interpretation of informative descriptors from QSAR models revealed pertinent knowledge on physicochemical properties governing the cytotoxic activities of tested cancer cell lines. It is anticipated that the QSAR models developed herein could provide guidelines for further development of novel and potent anticancer agents.
Letters in Drug Design & Discovery, 2013
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.
Bioorganic & Medicinal Chemistry, 2015
A series of 1,4-disubstituted-1,2,3-triazoles (13-35) containing sulfonamide moiety were synthesi... more A series of 1,4-disubstituted-1,2,3-triazoles (13-35) containing sulfonamide moiety were synthesized and evaluated for their aromatase inhibitory effects. Most triazoles with open-chain sulfonamide showed significant aromatase inhibitory activity (IC 50 = 1.3-9.4 lM). Interestingly, the meta analog of triazolebenzene-sulfonamide (34) bearing 6,7-dimethoxy substituents on the isoquinoline ring displayed the most potent aromatase inhibitory activity (IC 50 = 0.2 lM) without affecting normal cell. Molecular docking of these triazoles against aromatase revealed that the compounds could snugly occupy the active site of the enzyme through hydrophobic, p-p stacking, and hydrogen bonding interactions. The potent compound 34 was able to form hydrogen bonds with Met374 and Ser478 which were suggested to be the essential residues for the promising inhibition. The study provides compound 34 as a potential lead molecule of anti-aromatase agent for further development.
Open Access by Veda Prachayasittikul
Natural products have been an integral part of sustaining civilizations because of their medicina... more Natural products have been an integral part of sustaining civilizations because of their medicinal properties. Past discoveries of bioactive natural products have relied on serendipity, and these compounds serve as inspiration for the generation of analogs with desired physicochemical properties. Bioactive natural products with therapeutic potential are abundantly available in nature and some of them are beyond exploration by conventional methods. The effectiveness of computational approaches as versatile tools for facilitating drug discovery and development has been recognized for decades, without exception, in the case of natural products. In the post-genomic era, scientists are bombarded with data produced by advanced technologies. Thus, rendering these data into knowledge that is interpretable and meaningful becomes an essential issue. In this regard, computational approaches utilize the existing data to generate knowledge that provides valuable understanding for addressing current problems and guiding the further research and development of new natural-derived drugs. Furthermore, several medicinal plants have been continuously used in many traditional medicine systems since antiquity throughout the world, and their mechanisms have not yet been elucidated. Therefore, the utilization of computational approaches and advanced synthetic techniques would yield great benefit to improving the world’s health population and well-being.
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Papers by Veda Prachayasittikul
Open Access by Veda Prachayasittikul