Premium
Water‐soluble Schiff base Cu(II) and Zn(II) complexes: Synthesis, DNA targeting ability and chemotherapeutic potential of Cu(II) complex for hepatocellular carcinoma – in vitro and in vivo approach
Author(s) -
Pravin Narayanaperumal,
Kumaravel Ganesan,
Senthilkumar Raju,
Raman Natarajan
Publication year - 2017
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.3739
Subject(s) - chemistry , in vivo , hela , cytotoxicity , in vitro , apoptosis , dna , cell cycle , hepatic carcinoma , toxicity , hepatocellular carcinoma , cleavage (geology) , biochemistry , pharmacology , cancer research , organic chemistry , biology , microbiology and biotechnology , paleontology , fracture (geology)
Reliable compounds with low toxicity are tempting potential chemotherapeutics. With an aim of achieving less toxic but more potent metallodrugs, four new‐generation hydrophilic Cu(II) and Zn(II) complexes with DNA‐targeting properties were synthesized and characterized using various physicochemical data. The excellent DNA binding and cleavage results confirmed the mode of binding of DNA with the complexes and their ability to denature it. The profound in vitro cytotoxicity exhibited by complex 3 against a panel of cell lines (HeLa, MCF‐7 and HepG‐2) along with NHDF (normal human dermal fibroblasts) with distinct activity towards HepG‐2 and low toxicity to NHDF prompted in vivo studies of induced hepatocellular carcinoma‐affected Swiss albino rats. On evaluating various serum hepatic, biological and histopathological parameters, complex 3 showed excellent activity in restoring the damaged liver to normal. As a means of identifying the pathway of DNA damage, flow cytometric evaluation of cell cycle analysis was performed, which revealed S phase arrest‐induced apoptosis in HepG‐2 cells by complex 3 , making it a cell cycle‐specific drug.