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新型苯并噻二嗪基腙甲酰胺和苯并[1,2,4]噻二唑[1,5-b][1,2,4]噻二嗪-5,5-二酮的合成及抗癌活性。

Synthesis and anticancer activities of new Benzothiadiazinyl Hydrazinecarboxamides and Anilino[1,2,4]triazolo[1,5-b][1,2,4]thiadiazine 5,5-diones.

机构信息

Division of Organic Chemistry, Indian Institute of Chemical Technology, India.

出版信息

Med Chem. 2011 May;7(3):165-72. doi: 10.2174/157340611795564259.

Abstract

Two series of compounds (5-14 and 15-23) based on the scaffolds of 2-(1,1-dioxido-4-phenyl-4Hbenzo[e][1,2,4]thiadiazin-3-yl)-N-(4-methoxyphenyl)hydrazinecarboxamide (5) and 2-((4-methoxyphenyl)amino)-10-phenyl-10H-benzo[e][1,2,4]triazolo[1,5-b][1,2,4]thiadiazine 5,5-dioxide (15) respectively, were designed and synthesized. These compounds were tested for anticancer activity against various cancer cell lines including lung, ovary, prostate, breast and colon cancers. They exhibited moderate to good inhibitory activity against the above cell lines and compound 9 was found to be the most active one from these two series. Further studies showed that cancer cell growth inhibition by compounds 22 and 23 could be in part due to the inhibition of tubulin polymerization, with the IC50 values of 4.70 and 5.25 µM, respectively.

摘要

设计并合成了两个系列的化合物(5-14 和 15-23),它们分别基于 2-(1,1-二氧代-4-苯基-4H-苯并[e][1,2,4]噻二嗪-3-基)-N-(4-甲氧基苯基)肼甲酰胺(5)和 2-((4-甲氧基苯基)氨基)-10-苯基-10H-苯并[e][1,2,4]三唑并[1,5-b][1,2,4]噻二嗪 5,5-二氧化物(15)的骨架。这些化合物被测试了对包括肺癌、卵巢癌、前列腺癌、乳腺癌和结肠癌在内的各种癌细胞系的抗癌活性。它们对上述细胞系表现出中等至良好的抑制活性,并且化合物 9 是这两个系列中最活跃的化合物之一。进一步的研究表明,化合物 22 和 23 对癌细胞生长的抑制作用部分可能是由于微管蛋白聚合的抑制,其 IC50 值分别为 4.70 和 5.25µM。

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