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New Acetohydrazides Incorporating 2‐Oxoindoline and 4‐Oxoquinazoline: Synthesis and Evaluation of Cytotoxicity and Caspase Activation Activity
Author(s) -
Huan Le Cong,
Anh Duong Tien,
Truong Bui Xuan,
Duc Phan Huy,
Hai PhamThe,
DucAnh Lai,
Huong LeThiThu,
Park Eun Jae,
Lee Hye Jin,
Kang Jong Soon,
Tran PhuongThao,
Thanh Hai Dinh Thi,
Kim Oanh Dao Thi,
Han SangBae,
Nam NguyenHai
Publication year - 2020
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201900670
Subject(s) - chemistry , cytotoxicity , apoptosis , cytotoxic t cell , benzofuran , u937 cell , caspase , cancer research , necrosis , cancer cell , cell culture , caspase 3 , lung cancer , stereochemistry , cancer , biochemistry , microbiology and biotechnology , programmed cell death , medicine , in vitro , biology , genetics
In our search for new small molecules activating procaspase‐3, we have designed and synthesized a series of new acetohydrazides incorporating both 2‐oxoindoline and 4‐oxoquinazoline scaffolds. Biological evaluation showed that a number of these acetohydrazides were comparably or even more cytotoxic against three human cancer cell lines (SW620, colon cancer; PC‐3, prostate cancer; NCI−H23, lung cancer) in comparison to PAC‐1, a first procaspase‐3 activating compound, which was used as a positive control. One of those new compounds, 2‐(6‐chloro‐4‐oxoquinazolin‐3(4 H )‐yl)‐ N ′‐[(3 Z )‐5‐methyl‐2‐oxo‐1,2‐dihydro‐3 H ‐indol‐3‐ylidene]acetohydrazide activated the caspase‐3 activity in U937 human lymphoma cells by 5‐fold higher than the untreated control. Three of the new compounds significantly induced necrosis and apoptosis in U937 cells.