Abstract

SYNTHESIS, CHARACTERIZATION, DOCKING STUDIES, AND IN-VITRO CYTOTOXIC ACTIVITY OF SOME NOVEL SUBSTITUTED (3,5-DIMETHYL-1H-PYRAZOL-1-YL)(PHENYL)METHANONE DERIVATIVES

*Dr. N. Senthilkumar, K. Sumathi and Gokul T.

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Abstract

The novel set of substituted (3,5-dimethyl-1H-pyrazol-1-yl)(phenyl)methanone derivatives was designed and these compounds were subjected to docking studies against CDK and the result of docking studies revealed that all the compounds possess significant to moderate interaction with the targeted enzyme. Among the docked compounds, compound 17 possesses significant docking score -8.9 k/cal when compared to standard drug imatinib. And it shows 2 hydrogen bonds between the amino acids THR106 and HIS107. The remaining docked compound shows a docking score range from 7 to 9 k/cal along with one or two hydrogen bond interactions. Based on the docking score the derivatives 2, 4, 5, 6, 12, 14, 15, 16, 17, and 20 were selected for the synthesis by conventional method. These compounds were subjected to in-vitro cytotoxicity study by SRB assay method with cell lines MDA-MB-231 cell lines. Among the tested compounds, derivative 16 substituted with Dihydroxy benzene group shows a significant IC50 value (65.24 μg/ml) and followed by compound 15 substituted with chlorobenzene derivative (77.35 μg/ml) shows good inhibition in breast cancer cell line. Remaining all other tested compounds shows good to moderate cytotoxic activity on tested cell line.

Keywords: (3,5-dimethyl-1H-pyrazol-1-yl) (phenyl)methanone derivatives, docking study, CDK2, SRB assay, MDA-MB-231.