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

• Published in: Applied organometallic chemistry 2017-10, Vol.31 (10), p.n/a
• Main Authors: Pravin, Narayanaperumal, Kumaravel, Ganesan, Senthilkumar, Raju, Raman, Natarajan
• Format: Article
• Language: English
• Subjects: Apoptosis; Binding; Biocompatibility; Cell cycle; cell cycle arrest; Chemistry; Copper; cytotoxicity; Damage assessment; Damage detection; Deoxyribonucleic acid; DNA; DNA binding; Fibroblasts; Imines; In vivo methods and tests; Liver; Liver cancer; Rats; Rodents; Toxicity; water‐soluble Cu(II) complexes
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.3739

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. Reliable compounds with low toxicity are tempting potential chemotherapeutics. To achieve less toxic but more potent metallodrugs, four new hydrophilic Cu(II) and Zn(II) complexes with DNA‐targeting properties were synthesized and characterized. The binding and cleavage results confirmed the mode of binding of DNA with the complexes and their ability to denature it.