Remarkable visible light-triggered cytotoxicity of mitochondria targeting mixed-ligand cobalt(iii) complexes of curcumin and phenanthroline bases binding to human serum albumin. Issue 22 (9th February 2015)

• Record Type: Journal Article
• Authors: Sarkar, Tukki; Banerjee, Samya; Hussain, Akhtar
• Is Part Of: RSC advances. Volume 5:Issue 22(2015)
• Page Start: 16641
• Page End: 16653
• Publication Date: 2015-02-09
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c4ra17314g
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Co(iii ) complexes of curcumin and phenanthroline bases show remarkable visible-light induced cytotoxicity in HeLa cells but are much less toxic in dark and to normal cells. The complexes bind to HSA with significant affinity. Abstract : Six new mixed-ligand cobalt(iii ) complexes of formulation [Co( N – N )2 ( O – O )](ClO4 )2 (1–6 ), where N – N is a N, N -donor phenanthroline base, namely, 1, 10-phenanthroline (phen in1, 2 ), dipyrido[3, 2- d :2′, 3′- f ]quinoxaline (dpq in3, 4 ), and dipyrido[3, 2- a :2′, 3′- c ]phenazine (dppz in5, 6 ), O – O is acetylacetonate (acac in1, 3, 5 ) or curcumin (bis(4-hydroxy-3-methoxyphenyl)-1, 6-diene-3, 5-dione, cur in2, 4, 6 ), have been synthesized and characterized. The X-ray crystal structures of complex1 (as PF6 − salt, 1a ) and3 show distorted octahedral geometries formed by the CoN4 O2 core. The complexes1, 3 and5 having the simple acac ligand are prepared as control species to understand the role of curcumin. The optimized geometries and the frontier orbitals of the curcumin complexes2, 4, and6 are obtained from the DFT calculations. The complexes2, 4, and6 having the photoactive curcumin moiety display an absorption band in the visible region near 420 nm and show remarkable photocytotoxicity in HeLa cancer cells with respective IC50 values of 7.4 μM, 5.1 μM and 1.6 μM while being much less toxic in dark. MTT assay using complex6 shows that it is not significantly photocytotoxic to MCF-10A normal cells. The control complexes having the acac ligand are non-toxic both in the presence and absence of light. The cell death is apoptotic in nature and triggered by the photogeneration of reactive oxygen species. Fluorescence imaging experiments on HeLa cells reveals that complex6 accumulated primarily inside the mitochondria. Human serum albumin (HSA) binding experiments show that the complexes bind HSA with good affinity, but6 binds with the highest affinity, with a K b value of 9.8 × 10 5 M −1 . Thus, complex6 with its negligible toxicity in the dark and in normal cells but remarkable toxicity in visible light holds significant photochemotherapeutic potential.