Synthesis and biological evaluation of some novel pyrido[1,2-a]pyrimidin-4-ones as antimalarial agents.
Novel pyrido[1,2-a]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-a]pyrimidin-3-yl)carbamate (21, IC50 value 33 μM) and 4-Oxo-N-[4-(trifluoromethyl)benzyl]-4H-pyrido[1,2-a]pyrimidine-3-carboxamide (37, IC50 value 37 μM) showed moderate antimalarial activity. Cytotoxicity study was performed against mammalian cell line (Huh-7) by using the MTT assay for the moderately active compounds. Structural activity relationship (SAR) studies displayed that B-ring unsubstituted pyrido[1,2-a]pyrimidine scaffold is responsible for the antimalarial activities of the evaluated derivatives. This SAR based antimalarial screening supported that pyrido[1,2-a]pyrimidin-4-one can be considered as a lead heterocyclic structure for further development of more potent derivatives for antimalarial activity.
Pharmacy Department, Faculty of Tech. and Engg., The M. S. University of Baroda, Vadodara, 390 001 Gujarat, India; Torrent Research Centre, Village Bhat, Dist. Gandhinagar, 382421 Gujarat, India.
Uttam R
UR
Mane
Malaria Research Laboratory, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
D
D
Mohanakrishnan
Malaria Research Laboratory, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
Dinkar
D
Sahal
Pharmacy Department, Faculty of Tech. and Engg., The M. S. University of Baroda, Vadodara, 390 001 Gujarat, India.
Prashant R
PR
Murumkar
Pharmacy Department, Faculty of Tech. and Engg., The M. S. University of Baroda, Vadodara, 390 001 Gujarat, India.
Rajani
R
Giridhar
Pharmacy Department, Faculty of Tech. and Engg., The M. S. University of Baroda, Vadodara, 390 001 Gujarat, India. Electronic address: mryadav11@yahoo.co.in.
Mange Ram
MR
Yadav
D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D011744:Pyrimidinones
Antimalarial; Plasmodium falcsiparum; Pyrido[1,2-a]pyrimidin-4-one; SYBR Green Assay