Photo biological activation of NSO donor mixed-ligand complexes: In vivo and preclinical perspectives
•Synthesis of N, O and S donor mixed-ligand complexes having N-acetylcysteine.•Oxidative pathway involves H2O2 and 1O2 as the reactive oxygen species.•Efficient photo-nuclease activity upon irradiation with UV-A and visible light.•Enhanced photocytotoxicity against cancer cell lines but non-toxic to normal cells.
Pyrazolone incorporating N-acetylcysteine (NAC) mixed-ligand complexes are described as promising anti-inflammatory, anticonvulsant, SODs mimetic and cytotoxic compounds possibly due to its antioxidant profile. In this study, we have evaluated the pharmacologic activity, antioxidant and toxicological profiles of compounds (1–6). Among them, compounds 1 and 4 were haemobiocompatible than the others. Both complexes 1 and 4 display efficient photo-nuclease activity upon irradiation with UV-A light of 365 nm and red light of 647 nm as compared with others. Mechanistic studies reveal that the DNA cleavage oxidative pathway involves H2O2 and singlet oxygen as the reactive oxygen species. Interestingly, both compounds 1 and 4, show non-toxic effects in vitro to human normal lymphocyte cells, revealing that they are selective in killing only the cancer cells as expected for a better drug. In addition, considering the safety profile, these compounds are promising as preventive and/or therapeutic agents against oxidative damage.
Graphical abstractThe newly synthesized N-acetylcysteine amino acid mixed-ligand complexes exhibit more efficient photonuclease and cytotoxic effects than cisplatin and photofrin. Preclinical trials reveal that they are metal based chemotherapeutic agents.Figure optionsDownload full-size imageDownload as PowerPoint slide
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 138, 5 September 2014, Pages 256–272