Forezi Luana da S M, Tolentino Nathalia M C, de Souza Alessandra M T, Castro Helena C, Montenegro Raquel C, Dantas Rafael F, Oliveira Maria E I M, Silva Floriano P, Barreto Leilane H, Burbano Rommel M R, Abrahim-Vieira Bárbara, de Oliveira Riethe, Ferreira Vitor F, Cunha Anna C, Boechat Fernanda da C S, de Souza Maria Cecília B V
Outeiro de São João Batista, Fluminense FederalUniversity (UFF), s/n, Niterói 24020141, RJ, Brazil.
Laboratory of Molecular Modeling & QSAR (ModMolQSAR), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21949-900, RJ, Brazil.
Molecules. 2014 May 22;19(5):6651-70. doi: 10.3390/molecules19056651.
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.
作为持续寻找新的潜在抗癌候选物的一部分，我们描述了一系列4-氧代喹啉-3-甲酰胺衍生物作为新型抗癌剂的合成、细胞毒性及作用机制评估。使用MTT比色法测定了化合物10 - 18对三种癌细胞系的抑制活性。筛选结果显示，与临床使用的标准化疗药物阿霉素相比，衍生物16b和17b对胃癌细胞系表现出显著的细胞毒性活性，但对正常细胞系无活性。有趣的是，在测试16b和17b对血细胞的毒性时未观察到溶血活性。计算机模拟和体外作用机制评估表明，16b有潜力作为开发抗胃癌细胞新型抗癌剂的先导化合物。
