Design, synthesis and antitumor activity of a novel series of PAC-1 analogues

Hao-ming Luo; Chun-ling Yang; Xiao-ying Zhang; Ming-ming Zhao; Dan Jiang; Jun-hai Xiao; Xiao-hong Yang; Song Li

doi:10.1007/s40242-013-3336-8

Chemical Research in Chinese Universities ›› 2013, Vol. 29 ›› Issue (5) : 906 -910. DOI: 10.1007/s40242-013-3336-8

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Design, synthesis and antitumor activity of a novel series of PAC-1 analogues

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Abstract

A novel series of first procaspase activating compound(PAC-1) analogues was designed, synthesized and evaluated for antitumor activity towards two cell lines[human promyelocytic leukemia cell line(HL60) and human embryonic lung fibroblast cell line(HLF)] by the MTT[3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazo-liumromide]_method in vitro. The structures of all the compounds were confirmed by ¹H NMR, MS and elemental analysis. Among the compounds synthesized,(E)-2-[(3-{[4-(tert-butyl)benzyl](methyl)amino}propyl)(methyl)amino]-N′-[4-(diethylamino)-2-hydroxybenzylidene]acetohydrazide(compound 6n) exhibits a good anti-proliferative activity to the majority of tumor cells tested, and selectively cleaves cancer cells. Thus, compound 6n was identified as promising lead compound for further structural modification.

Keywords

PAC-1 analogue / Anticancer activity / MTT assay / HL60

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Hao-ming Luo, Chun-ling Yang, Xiao-ying Zhang, Ming-ming Zhao, Dan Jiang, Jun-hai Xiao, Xiao-hong Yang, Song Li. Design, synthesis and antitumor activity of a novel series of PAC-1 analogues. Chemical Research in Chinese Universities, 2013, 29(5): 906-910 DOI:10.1007/s40242-013-3336-8

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