Design, synthesis, and evaluation of novel N'-substituted-1-(4-chlorobenzyl)-1H-indol-3-carbohydrazides as antitumor agents. (1st January 2020)

• Record Type: Journal Article
• Authors: Huan, Le Cong; Anh, Duong Tien; Hai, Pham-The; Anh, Lai Duc; Park, Eun Jae; Ji, A Young; Kang, Jong Soon; Dung, Do Thi Mai; Oanh, Dao Thi Kim; Tung, Truong Thanh; Hai, Dinh Thi Thanh; Han, Sang-Bae; Nam, Nguyen-Hai
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 35:Number 1(2020)
• Page Start: 1854
• Page End: 1865
• Publication Date: 2020-01-01
• Subjects: Acetohydrazides -- isatin -- cytotoxicity -- caspase activation; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2020.1816997
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: In continuity of our search for novel anticancer agents acting as procaspase activators, we have designed and synthesised two series of ( E )- N ′ - benzylidene-carbohydrazides (4a–m ) and (Z)-N' -(2-oxoindolin-3-ylidene)carbohydrazides (5a–g ) incorporating 1-(4-chlorobenzyl)-1 H -indole core. Bioevaluation showed that the compounds, especially compounds in series 4a–m, exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). Within series 4a–m, compounds with 2-OH substituent (4g–i ) exhibited very strong cytotoxicity in three human cancer cell lines assayed with IC50 values in the range of 0.56–0.83 µM. In particular, two compounds 4d and 4f bearing 4-Cl and 4-NO2 substituents, respectively, were the most potent in term of cytotoxicity with IC50 values of 0.011–0.001 µM. In caspase activation assay, compounds 4b and 4f were found to activate caspase activity by 314.3 and 270.7% relative to PAC-1. This investigation has demonstrated the potential of these simple acetohydrazides, especially compounds 4b, 4d, and 4f, as anticancer agents.