Zinc (II) complex with a cationic Schiff base ligand: synthesis, characterization, and biological studies.
A cationic Schiff base ligand, TSB (L) and its Zn (II) complex (1) were synthesized and characterized by using CHN, (1)H-NMR, FT-IR, UV, LC-MS, and X-ray methods. Their ability to inhibit topoisomerase I, DNA cleavage activities, and cytotoxicity were studied. X-ray diffraction study shows that the mononuclear complex 1 is four coordinated with distorted tetrahedral geometry. The singly deprotonated Schiff base ligand L acts as a bidentate ON-donor ligand. Complexation of L increases the inhibitory strength on topoisomerase I activity. Complex 1 could fully inhibit topoisomerase I activity at 250 μM, while L did not show any inhibitory effect on topoisomerase I activity. In addition, L and complex 1 could cleave pBR322 DNA in a concentration and time dependent profile. Surprisingly, L has better DNA cleavage activity than complex 1. The cleavage of DNA by complex 1 is altered in the presence of hydrogen peroxide. Furthermore, L and complex 1 are mildly cytotoxic towards human ovarian cancer A2780 and hepatocellular carcinoma HepG2.
Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Sze Koon
SK
Lee
Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: kongwai@um.edu.my.
Kong Wai
KW
Tan
Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia; Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia.
Seik Weng
SW
Ng
Department of Biomedical Sciences, Universiti Putra Malaysia, 43400 Serdang, Malaysia.
Kah Kooi
KK
Ooi
Department of Biomedical Sciences, Universiti Putra Malaysia, 43400 Serdang, Malaysia.
Kok Pian
KP
Ang
Department of Biomedical Sciences, Universiti Putra Malaysia, 43400 Serdang, Malaysia.
Md Akim
MA
Abdah
D002412:Cations; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004583:Electrons; D004587:Electrophoresis, Agar Gel; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D012545:Schiff Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D059003:Topoisomerase Inhibitors / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology* / Q000633:toxicity
D002412:Cations; D008024:Ligands; D012545:Schiff Bases; D059003:Topoisomerase Inhibitors; D004264:DNA Topoisomerases, Type I; D015032:Zinc
Cytotoxicity; DNA cleavage; Schiff base; Topoisomerase I; Zinc