DIHYDROPYRIMIDINONE DERIVED CHALCONES AS EMERGING ANTICANCER SCAFFOLDS AGAINST A549 LUNG CANCER CELL LINES

Abstract

Novel dihydropyrimidnone chalcones were synthesized by using Clasein Schmidth condensation from 5-acetyl, 6-methyl, 4- (3- ethoxy, 4-hydroxy phenyl) dihyro pyrimidine-2-one by reacting with various substituted aldehydes.  Their structural characterizations were evaluated by FT-IR, 1H NMR, 13C NMR, mass spectroscopy. They were screened for in vitro anticancer activity by using MTT assay against human lung cancercell lines (A-549). Dihydropyrimidnone chalcones CH4 (21± 2), CH13 (23± 2) and CH15 (18± 2) showed nearly equal potent with the standard drug Methothrexate (11± 2). Docking was done with crystalline protein structure of SAMDH1 which has rapid gene expression in lung cancer cell than other cancer cells.  Amino acid residues GLY-159, ARG-160, ASP-94, TYR-39, GLY-40, HIS-53, of SAMHD1 were found to be directly interacting with the synthesized compounds. The most active compounds with dock scores (Kcal/mol) are as CH4= - 8.3, CH13 = -8.7, CH15 compared to Methothrexate (-6.10 kcal/mol) and these results have correlated with in vitro MIC values.  Hence, these novel dihydropyrimidinone chalcones were considered as lead anti-cancer agents against lung cancer.