Synthesis, cytotoxicity and mechanistic evaluation of 4-oxoquinoline-3-carboxamide derivatives: finding new potential anticancer drugs

4-氧代喹啉-3-酰胺衍生物的合成、细胞毒性及机理评价:寻找新的潜在抗癌药物

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作者:Luana da S M Forezi, Nathalia M C Tolentino, Alessandra M T de Souza, Helena C Castro, Raquel C Montenegro, Rafael F Dantas, Maria E I M Oliveira, Floriano P Silva Jr, Leilane H Barreto, Rommel M R Burbano, Bárbara Abrahim-Vieira, Riethe de Oliveira, Vitor F Ferreira, Anna C Cunha, Fernanda da C S B

Abstract

As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10-18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.

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