Synthesis and Anticancer Activities of New Benzothiadiazinyl Hydrazinecarboxamides and Anilino[1,2,4]triazolo[1,5-b][1,2,4]thiadiazine 5,5-diones

Ahmed      Kamal; Y.      V.V. Srikanth; Md.      Ashraf; M.      Naseer A. Khan; Thokhir      Basha Shaik; Shasi      V. Kalivendi; Nitasha      Suri; A.      K. Saxena

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.

Keywords: Hydrazinecarboxamides, triazolo benzothiadiazines, anticancer activity, tubulin polymerization, cancer cell lines, colon cancers, Tubulin Polymerization Assay, 2-(1,1-dioxido-4-phenyl-4Hbenzo[e][1,2,4]thiadiazin-3-yl)-N-(4-methoxyphenyl)hydrazinecarboxamide, 2-((4-methoxyphenyl)amino)-10-phenyl-10H-benzo[e][1,2,4]triazolo[1,5-b][1,2,4]thiadiazine 5,5-dioxide, Breast cancers, Lung Cancer