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

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 35; no. 1; pp. 1854 - 1865
• Main 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
• Format: Journal Article
• Language: English
• Published: England 01.12.2020
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Caspase Inhibitors - chemical synthesis; Caspase Inhibitors - pharmacology; Caspases, Initiator - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Humans; Hydrazines - chemical synthesis; Hydrazines - pharmacology; Isatin - chemistry; Molecular Docking Simulation; Structure-Activity Relationship; Acetohydrazides; isatin; cytotoxicity; caspase activation
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2020.1816997

In continuity of our search for novel anticancer agents acting as procaspase activators, we have designed and synthesised two series of ( )- ' benzylidene-carbohydrazides ( ) and -(2-oxoindolin-3-ylidene)carbohydrazides ( ) incorporating 1-(4-chlorobenzyl)-1 -indole core. Bioevaluation showed that the compounds, especially compounds in series , exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). Within series , compounds with 2-OH substituent ( ) exhibited very strong cytotoxicity in three human cancer cell lines assayed with IC values in the range of 0.56-0.83 µM. In particular, two compounds and bearing and 4-NO substituents, respectively, were the most potent in term of cytotoxicity with IC values of 0.011-0.001 µM. In caspase activation assay, compounds and 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 , , and , as anticancer agents.