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Synthesis and antitumor activity of 2‐isocamphanyl thiosemicarbazone derivatives via ROS‐enhanced mitochondrial damage
Author(s) -
Wang Yunyun,
Wang Zhonglong,
Kuang Hongbo,
Zhang Yan,
Gu Wen,
Zhu Yongqiang,
Wang Shifa
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13492
Subject(s) - apoptosis , chemistry , reactive oxygen species , in vitro , cancer cell , cytotoxic t cell , a549 cell , cell culture , semicarbazone , caspase , mitochondrion , caspase 3 , stereochemistry , pharmacology , biochemistry , programmed cell death , cancer , biology , genetics
A series of novel 2‐isocamphanyl thiosemicarbazone derivatives were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. In in vitro anticancer activity, most derivatives showed considerable cytotoxic activity against four cancer cell lines (RPMI‐8226, A549, MDA‐MB‐231, and HepG2 cancer cells) and showed low toxicity against human gastric mucosal cells (GES‐1). Among them, compound 4h exhibited excellent antitumor activity against the tested cancer cells with IC 50 values of 0.4, 1.1, 1.6, and 1.7 μM for MDA‐MB‐231, RPMI‐8226, A549, and HepG2, respectively. Further, mechanism studies indicated that compound 4h induced apoptosis in MDA‐MB‐231 cells through enhancing reactive oxygen species levels, inducing mitochondrial membrane potential decrease, and influencing the expression of Bax, Bcl‐2, caspase‐3, and caspase‐9.