Radhika Chelamalla* and Ajitha Makula Pages 1172 - 1180 ( 9 )
Background: Progress in the developments of pyrimidine-coumarin moiety as an IDO inhibitor is still continuing with an outcome of the good scaffold as pyrimidine as well as coumarin individually for anticancer activity. Hence we proposed a suitable approach for the synthesis of pyrimidinecoumarin moieties in a combined form from the results of docking studies.Objective: As part of our ongoing research towards the development of novel cytotoxic agents, the synthesis and cytotoxic activity of a series of N'-(1-(6-methyl-2-oxo/thioxo-4-sub phenyl-1,2,3,4- tetrahydropyrimidin-5-yl)vinyl)-2-oxo-2H-chromene-3-carbohydrazide derivatives are discussed in this study. Methods: N'-(1-(6-methyl-2-oxo/thioxo-4-sub phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)vinyl)-2-oxo- 2H-chromene-3-carbohydrazide derivatives were designed, synthesized and evaluated for cytotoxic activity. The structures were confirmed by IR, 1H NMR, C13NMR, Mass spectroscopy. All the synthesized compounds were evaluated using in vitro MTT assay against HeLa and HepG2 cell lines. Results: Compound 6g showed inhibitory activity against IDO with IC50 values at nanomolar range in docking studies and compounds 6g and 6f also showed significant cytotoxic activity on human cancer cell lines like HepG2 and HeLa using in vitro MTT assay. Conclusion: This work showed that the coumarin containing pyrimidine derivatives are found to be the most potent against IDO through docking studies and cytotoxic against cell lines compared with cisplatin. This might give the information for the development of new series of compounds against IDO.
Coumarin, pyrimidine, indolamine-2, 3-dioxygensase, docking, cytotoxic activity, MTT assay.
Centre for Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad-500085, TS, Centre for Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad-500085, TS