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4,6-diaryl Pyrimidones as Constrained Chalcone Analogues: Design, Synthesis and Evaluation as Antiproliferative

Dinesh Kumar, Kunal Nepali¹, P M S Bedi

¹Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab-143005. kunal_8855@rediffmail.com.

Anti-Cancer Agents in Medicinal Chemistry

|March 19, 2015

Abstract:

4,6-diarylpyrimidones as constrained chalcone analogues have been synthesised in the present study. The synthesised compounds were evaluated against a panel of human cancer cell lines. Striking selectivity was displayed by the compounds against MiaPaCa (Pancreatic) cell lines while PC-3 (prostate) and A-549 (lung) cell lines were almost resistant to the exposure of the test compounds. Compound SK - 25 exhibited remarkable cytotoxicity against MiaPaca-2 cell line with an IC50 value of 1.95 µM and was found to induce apoptosis evidenced through phase contrast microscopy, DAPI staining and mitochondrial membrane potential loss. The cell phase distribution studies indicated that the apoptotic population increased from 1.79% in control sample to 30.33 % in sample treated with 20 µM compound SK-25.

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