title: 4,6-diaryl Pyrimidones as Constrained Chalcone Analogues: Design, Synthesis and Evaluation as Antiproliferative Agents.
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.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab-143005. kunal_8855@rediffmail.com.
authors.forename: Kunal
authors.initials: K
authors.lastname: Nepali
authors.forename: P M S
authors.initials: PM
authors.lastname: Bedi
authors.forename: Suresh
authors.initials: S
authors.lastname: Kumar
authors.forename: Fayaz
authors.initials: F
authors.lastname: Malik
authors.forename: Subheet
authors.initials: S
authors.lastname: Jain
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002599:Chalcone / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011744:Pyrimidinones; D002599:Chalcone