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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Karande, Anjali A. Anbu, Sellamuthu Kandaswamy, Muthusamy Ravishankaran, Rajendran
Description	Author Affiliation: Anbu S ( Department of Inorganic Chemistry, University of Madras, Guindy Maraimalai Campus, Chennai-600 025, India.)
Abstract	A series of macrobicyclic dizinc(II) complexes $[Zn_{2}L^{1–2}B](ClO_{4})_{4}$ (1–6) have been synthesized and characterized $(L^{1–2}$ 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 × $10^{5}$ to 5.25 × $10^{5}$ $M^{−1},$ 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 $(k_{obs})$ of 5.56 ± 0.1 and 5.12 ± 0.2 $h^{−1},$ respectively, showing a $10^{7}-fold$ 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.
ISSN	14779226
Issue Number	41
Volume Number	41
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2012-11-07
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Antineoplastic Agents Pharmacology Coordination Complexes DNA Metabolism Zinc Chemistry Carcinoma Drug Therapy Caspase 3 Caspase 9 Cell Line, Tumor Cell Proliferation Drug Effects Cell Survival DNA Cleavage HeLa Cells Humans L-Lactate Dehydrogenase Neoplasms Serum Albumin, Bovine Journal Article Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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