Affiliations 

  • 1 Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 2 Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: kongwai@um.edu.my
  • 3 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
  • 4 Department of Biomedical Sciences, Universiti Putra Malaysia, 43400 Serdang, Malaysia
PMID: 24231745 DOI: 10.1016/j.saa.2013.10.084

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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