Copper(II) complexes of terpyridine derivatives: a footstep towards development of antiproliferative agent for breast cancer.
Two copper(II) complexes with terpyridyl conjugates, [Cu(meotpy)(dmp)](NO(3))(2) (1) and [Cu(bitpy)(dmp)](NO(3))(2) (2) where meotpy, bitpy and dmp stand for methoxybenzyl terpyridine, benzimidazolyl terpyridine and dimethyl phenanthroline respectively have been synthesized and characterized. Complex 1 has also been characterized crystallographically. Both the complexes have been found to bind CT-DNA intercalatively. The ability of these complexes to bring about DNA cleavage has been analyzed using gel electrophoresis. Both complexes 1 and 2 have been found to bring about hydrolytic cleavage of DNA. The cytotoxicity of both these complexes has been tested against cancerous as well as non-cancerous cell lines. Towards non-cancerous cell line complex 2 exhibited very low toxicity. On the other hand both the complexes have been found to exhibit cytotoxic effects against cancerous cell lines. Complex 2 which has lower IC(50), was found to be a potent antiproliferative agent against MCF-7 cells and was able to induce mitochondrial-mediated and caspase-dependent apoptosis with increase in G(0)/G(1) and subsequent arrest in the S phase, in cell cycle progression. Based on this study, it is hypothesized that 2 may be a suitable candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancer.
Chemical Laboratory, Central Leather Research Institute, Council of Scientific and Industrial Research, Adyar, Chennai-600 020, Tamil Nadu, India.
Subramaniyam
S
Rajalakshmi
Thomas
T
Weyhermüller
Murugan
M
Dinesh
Balachandran Unni
BU
Nair
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper; D018360:Crystallography, X-Ray; D053837:DNA Cleavage; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D016196:S Phase; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D056831:Coordination Complexes; D011725:Pyridines; D003300:Copper