title: Design, synthesis and in vitro evaluation of 18β-glycyrrhetinic acid derivatives for anticancer activity against human breast cancer cell line MCF-7.
abstract: In the present work, QSAR model was derived by multiple linear regression method for the prediction of anticancer activity of 18β-glycyrrhetinic acid derivatives against the human breast cancer cell line MCF-7. The QSAR model for anti-proliferative activity against MCF-7 showed high correlation (r(2)=0.90 and rCV(2)=0.83) and indicated that chemical descriptors namely, dipole moment (debye), steric energy (kcal/mole), heat of formation (kcal/mole), ionization potential (eV), LogP, LUMO energy (eV) and shape index (basic kappa, order 3) correlate well with activity. The QSAR virtually predicted that active derivatives were first semi-synthesized and characterized on the basis of their (1)H and (13)C NMR spectroscopic data and then were in-vitro tested against MCF-7 cancer cell line. In particular, octylamide derivative of glycyrrhetinic acid GA-12 has marked cytotoxic activity against MCF-7 similar to that of standard anticancer drug paclitaxel. The biological assays of active derivative selected by virtual screening showed significant experimental activity.
authors.forename: Dharmendra Kumar
authors.initials: DK
authors.lastname: Yadav
authors.forename: Komal
authors.initials: K
authors.lastname: Kalani
authors.forename: Abhishek K
authors.initials: AK
authors.lastname: Singh
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Srivastava
authors.affiliation: Metabolic & Structural Biology Department, 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: Aditya B
authors.initials: AB
authors.lastname: Pant
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid