title: Pharmacophore based 3D-QSAR study of biphenyl derivatives as nonsteroidal aromatase inhibitors in JEG-3 cell lines.
abstract: Breast cancer is one of the most high-profile malignant diseases in modern society. Among postmenopausal women affected by the disease, a substantial portion has breast tumors that are estrogen-receptor positive. A common therapeutic intervention for this type of cancer is through endocrine therapy. Endocrine agents can act by either diminishing the availability or inhibiting the binding of estrogens to ER. Aromatase catalyzes the conversion of androgens to estrogens in the final step of the biosynthesis of estrogens and is therefore an attractive therapeutic target for inhibition. 3DQSAR pharmacophore modeling studies were undertaken for biphenyl derivatives as aromatase inhibitors in JEG-3 cell lines. A four-point pharmacophore with two H-bond acceptors and two aromatic rings as pharmacophoric features was developed. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of R² = 0.977 for training set molecules. The generated model showed excellent predictive power, with a correlation coefficient of Q² = 0.946 for an external test set. The 3D-QSAR plots illustrated insights into the structure activity relationship of these compounds which may help in the design and development of potent biphenyl derivatives as new aromatase inhibitors.
authors.affiliation: Professor of Pharmaceutical Chemistry, University College of Pharmaceutical Sciences and Centre under Special Assistance Programme (UGC-SAP), Kakatiya University, Warangal, A.P. 506 009, India. raghumed@kakatiya.ac.in.
authors.forename: Lakshmi Narayana
authors.initials: LN
authors.lastname: Bheemanapalli
authors.forename: C
authors.initials: C
authors.lastname: Balakumar
authors.forename: Venkat Rao
authors.initials: VR
authors.lastname: Kaki
authors.forename: Rajwinder
authors.initials: R
authors.lastname: Kaur
authors.forename: Raghuram Rao
authors.initials: RR
authors.lastname: Akkinepally
mesh_terms: D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D047072:Aromatase Inhibitors; D001713:Biphenyl Compounds; D004968:Estrogens, Non-Steroidal; C010574:biphenyl