Pharmacophore based 3D-QSAR study of biphenyl derivatives as nonsteroidal aromatase inhibitors in JEG-3 cell lines.

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.

QSAR of adenosine receptor antagonists: Exploring physicochemical requirements for binding of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives with human adenosine A(3) receptor subtype.

Human adenosine A(3) receptor (A(3) AR) binding affinity of pyrazolotriazolopyrimidine derivatives (n=116) has been subjected to QSAR analyses using three-dimensional (shape, spatial, electronic, and molecular field) along with thermodynamic descriptors to explore the physicochemical requirements for the binding. QSAR models have been validated internally [using leave-one-out cross-validation method] and externally [using test set molecules] to ensure the predictive capacity of the models. The models suggest that shape of the substituent at N(8) position of the pyrazole ring should be optimum. Furthermore, lipophilic substituents having electronegative atoms at NH(2) group of C(5) position of the pyrimidine ring with distributed negative charge over the surface may enhance the binding affinity. Again, the carbamoylation of the NH(2) group at C(5) position of pyrimidine ring is an essential factor for binding with A(3) receptor. The QSAR models were used for the design and development of some novel thienopyrimidines which were predicted to have good affinity towards A(3) AR.

Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines.

A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies.