Synthesis and biological evaluation of some novel pyrido[1,2-a] pyrimidin-4-ones as antimalarial agents

Novel pyrido[1,2-alpha]pyrimidin-4-ones have been synthesized and evaluated for their antimalarial activity by SYBR Green I assay against erythrocytic stages of chloroquine (CQ) sensitive Pf 3D7 strain. The antimalarial screening of 42 different compounds revealed that 3-Fluorobenzyl(4-oxo-4H-pyrido [1,2-alpha] pyrimidin-3-yl)carbamate (21, IC50 value 33 mu M) and 4-Oxo-N[4-(trifluoromethyl)benzy11-4H-pyrido 11,2-alpha]pyrimidine-3-carboxamide (37, IC50 value 37 mu M) showed moderate antimalarial activity. Cytotoxicity study was performed against mammalian cell line (Huh-7) by using the MIT assay for the moderately active compounds. Structural activity relationship (SAR) studies displayed that B-ring unsubstituted pyrido[1,2-alpha]pyrimidine scaffold is responsible for the antimalarial activities of the evaluated derivatives. This SAR based antimalarial screening supported that pyrido[1,2-alpha]pyrimidin-4-one can be considered as a lead heterocyclic structure for further development of more potent derivatives for antimalarial activity.(c) 2014 Elsevier Masson SAS. All rights reserved.