Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

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

LUO Hao-ming^1,2, YANG Chun-ling², ZHANG Xiao-ying³, ZHAO Ming-ming⁴, JIANG Dan², XIAO Jun-hai², YANG Xiao-hong¹, LI Song²

1. School of Pharmaceutical Sciences, Jilin University, Changchun 130021, P. R. China;
2. National Engineering Research Center for the Strategic Drugs, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P. R. China;
3. The First Hospital of Jilin University, Changchun 130021, P. R. China;
4. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

Received:2013-08-06 Revised:2013-08-30 Online:2013-10-01 Published:2013-09-17
Contact: XIAO Jun-hai, YANG Xiao-hong E-mail:xiaojunhai@139.com;xiaohongyang88@126.com
Supported by:
Supported by the National Natural Science Foundation of China(Nos.20771030, 20671025).

Abstract

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.

Key words: PAC-1 analogue, Anticancer activity, MTT assay, HL60

LUO Hao-ming, YANG Chun-ling, ZHANG Xiao-ying, ZHAO Ming-ming, JIANG Dan, XIAO Jun-hai, YANG Xiao-hong, LI Song. Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues[J]. Chemical Research in Chinese Universities, 2013, 29(5): 906-910.

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Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

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