A series of novel 6,8-dibromo-2-aryl-2,3-dihydroquinolin-4(1H)-ones have been synthesized and evaluated in vitro (in MCF-7 breast cancer cell lines). Compounds 5a, 5d, 5e, and 5g exhibited potent GI 50 and TGI values compared with reference standard and compounds 5b and 5c showed moderate activity. The docking studies (in silico) were conducted to recognize the hypothetical binding motif of the title compounds within the active site of aromatase enzyme employing GOLD docking software. The binding mode and SAR of the title compounds has been proposed based on the docking studies.

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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.

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Fused pyrimidine derivatives R 0515Synthesis and Antibacterial Activity of a New Series of 2,3,5,7-Substituted-pyrido[2,3-d]pyrimidin-4(3H)-one Derivatives. -An alternative route to key intermediates (III) via aminolysis of 2-bromonicotinamides, which are obtained upstream by a two-step procedure, is also described. However, yields are appreciably lower compared to the EDC coupling method. All new heterocycles (V) are screened for their antibacterial activity against Gram-positive and Gram-negative bacteria and are found to be active. -(BHEEMANAPALLI, L. N.; AKKINEPALLY*, R. R.; PAMULAPARTHY, S. R.; Chem. Pharm. Bull. 56 (2008) 9, 1342-1348; Univ. Inst. Pharm. Sci., Panjab Univ., Chandigarh 160 014, India; Eng.) -H. Haber 09-158