Jump to main content
Jump to site search

Issue 41, 2012
Previous Article Next Article

DNA targeting polyaza macrobicyclic dizinc(II) complexes promoting high in vitro caspase dependent anti-proliferative activity against human carcinoma cancer cells

Author affiliations

Abstract

A series of macrobicyclic dizinc(II) complexes [Zn2L1–2B](ClO4)4 (1–6) have been synthesized and characterized (L1–2 are polyaza macrobicyclic binucleating ligands, and B is the N,N-donor heterocyclic base (viz. 2,2′-bipyridine (bipy) and 1,10-phenanthroline (phen)). The DNA and protein binding, DNA hydrolysis and anticancer activity of these complexes were investigated. The interactions of complexes 1–6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence and CD spectroscopy. The DNA binding constant values of the complexes were found to range from 2.80 × 105 to 5.25 × 105 M−1, and the binding affinities are in the following order: 3 > 6 > 2 > 5 > 1 > 4. All the dizinc(II) complexes 1–6 are found to effectively promote the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 3 and 6 under physiological conditions give observed rate constants (kobs) of 5.56 ± 0.1 and 5.12 ± 0.2 h−1, respectively, showing a 107-fold rate acceleration over the uncatalyzed reaction of dsDNA. Remarkably, the macrobicyclic dizinc(II) complexes 1–6 bind and cleave bovine serum albumin (BSA), and effectively promote the caspase-3 and caspase-9 dependent deaths of HeLa and BeWo cancer cells. The cytotoxicity of the complexes was further confirmed by lactate dehydrogenase enzyme levels in cancer cell lysate and content media.

Graphical abstract: DNA targeting polyaza macrobicyclic dizinc(ii) complexes promoting high in vitro caspase dependent anti-proliferative activity against human carcinoma cancer cells

Back to tab navigation

Supplementary files

Publication details

The article was received on 21 May 2012, accepted on 29 Aug 2012 and first published on 29 Aug 2012


Article type: Paper
DOI: 10.1039/C2DT31094E
Citation: Dalton Trans., 2012,41, 12970-12983
  •   Request permissions

    DNA targeting polyaza macrobicyclic dizinc(II) complexes promoting high in vitro caspase dependent anti-proliferative activity against human carcinoma cancer cells

    S. Anbu, R. Ravishankaran, A. A. Karande and M. Kandaswamy, Dalton Trans., 2012, 41, 12970
    DOI: 10.1039/C2DT31094E

Search articles by author

Spotlight

Advertisements