title: QSAR and docking studies on xanthone derivatives for anticancer activity targeting DNA topoisomerase IIα.
abstract: Due to the high mortality rate in India, the identification of novel molecules is important in the development of novel and potent anticancer drugs. Xanthones are natural constituents of plants in the families Bonnetiaceae and Clusiaceae, and comprise oxygenated heterocycles with a variety of biological activities along with an anticancer effect. To explore the anticancer compounds from xanthone derivatives, a quantitative structure activity relationship (QSAR) model was developed by the multiple linear regression method. The structure-activity relationship represented by the QSAR model yielded a high activity-descriptors relationship accuracy (84%) referred by regression coefficient (r(2)=0.84) and a high activity prediction accuracy (82%). Five molecular descriptors - dielectric energy, group count (hydroxyl), LogP (the logarithm of the partition coefficient between n-octanol and water), shape index basic (order 3), and the solvent-accessible surface area - were significantly correlated with anticancer activity. Using this QSAR model, a set of virtually designed xanthone derivatives was screened out. A molecular docking study was also carried out to predict the molecular interaction between proposed compounds and deoxyribonucleic acid (DNA) topoisomerase IIα. The pharmacokinetics parameters, such as absorption, distribution, metabolism, excretion, and toxicity, were also calculated, and later an appraisal of synthetic accessibility of organic compounds was carried out. The strategy used in this study may provide understanding in designing novel DNA topoisomerase IIα inhibitors, as well as for other cancer targets.
authors: Metabolic and Structural Biology Department, Central Institute of Medicinal and Aromatic Plants, Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, India.
authors: Sarfaraz
authors: S
authors: Alam
authors: Metabolic and Structural Biology Department, Central Institute of Medicinal and Aromatic Plants, Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, India.
authors: Feroz
authors: F
authors: Khan
mesh_terms: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D016014:Linear Models; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D044004:Xanthones; D004250:DNA Topoisomerases, Type II
keywords: ADMET; HeLa cell line; drug likeness; regression model