Mane Uttam R, Mohanakrishnan D, Sahal Dinkar, Murumkar Prashant R, Giridhar Rajani, Yadav Mange Ram
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.
Malaria Research Laboratory, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
Eur J Med Chem. 2014 May 22;79:422-35. doi: 10.1016/j.ejmech.2014.04.031. Epub 2014 Apr 13.
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.
已合成新型吡啶并[1,2 - a]嘧啶 - 4 - 酮，并通过SYBR Green I分析法针对氯喹（CQ）敏感的Pf 3D7株红细胞阶段评估其抗疟活性。对42种不同化合物的抗疟筛选显示，3 - 氟苄基（4 - 氧代 - 4H - 吡啶并[1,2 - a]嘧啶 - 3 - 基）氨基甲酸酯（21，IC50值为33 μM）和4 - 氧代 - N - [4 - （三氟甲基）苄基] - 4H - 吡啶并[1,2 - a]嘧啶 - 3 - 甲酰胺（37，IC50值为37 μM）表现出中等抗疟活性。通过MTT分析法对中等活性化合物针对哺乳动物细胞系（Huh - 7）进行细胞毒性研究。构效关系（SAR）研究表明，B环未取代的吡啶并[1,2 - a]嘧啶支架是所评估衍生物抗疟活性的原因。这种基于SAR的抗疟筛选支持吡啶并[1,2 - a]嘧啶 - 4 - 酮可被视为用于进一步开发更有效抗疟活性衍生物的先导杂环结构。
