Photo biological activation of NSO donor mixed-ligand complexes: In vivo and preclinical perspectives

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2014-09, Vol.138, p.256-272
• Main Authors: Selvaganapathy, Muthusamy, Pravin, Narayanaperumal, Pothiraj, Krishnan, Raman, Natarajan
• Format: Article
• Language: English
• Subjects: Animals; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bacteria - drug effects; Behavior, Animal - drug effects; Cell Line; Cell Survival - drug effects; Cell Survival - radiation effects; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Coordination Complexes - therapeutic use; DNA Cleavage - drug effects; DNA Cleavage - radiation effects; Edema - chemically induced; Edema - drug therapy; Fungi - drug effects; Humans; Ligands; Light; Lymphocytes - drug effects; Lymphocytes - radiation effects; Microbial Sensitivity Tests; N-acetylcysteine; Non-toxic effects; Photo-nuclease activity; Rats; Seizures - chemically induced; Seizures - drug therapy; Therapeutic agents; Ultraviolet Rays
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2014.06.003

The 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. [Display omitted] •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 365nm and red light of 647nm 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.