title: QSAR and docking based semi-synthesis and in vitro evaluation of 18 β-glycyrrhetinic acid derivatives against human lung cancer cell line A-549.
abstract: For the prediction of anticancer activity of glycyrrhetinic acid (GA-1) analogs against the human lung cancer cell line (A-549), a QSAR model was developed by forward stepwise multiple linear regression methodology. The regression coefficient (r(2)) and prediction accuracy (rCV(2)) of the QSAR model were taken 0.94 and 0.82, respectively in terms of correlation. The QSAR study indicates that the dipole moments, size of smallest ring, amine counts, hydroxyl and nitro functional groups are correlated well with cytotoxic activity. The docking studies showed high binding affinity of the predicted active compounds against the lung cancer target EGFR. These active glycyrrhetinic acid derivatives were then semi-synthesized, characterized and in-vitro tested for anticancer activity. The experimental results were in agreement with the predicted values and the ethyl oxalyl derivative of GA-1 (GA-3) showed equal cytotoxic activity to that of standard anticancer drug paclitaxel.
authors.affiliation: Department of Metabolic and Structural Biology, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O.-CIMAP, Kukrail Picnic Spot Road, Lucknow-226015 (U.P.), India. f.khan@cimap.res.in.
authors.forename: Dharmendra Kumar
authors.initials: DK
authors.lastname: Yadav
authors.forename: Komal
authors.initials: K
authors.lastname: Kalani
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Srivastava
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid