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Remarkable photocytotoxicity in hypoxic HeLa cells by a dipyridophenazine copper(II) Schiff base thiolate

Lahiri, Debojyoti and Majumdar, Ritankar and Mallick, Dibyendu and Goswami, Tridib K and Dighe, Rajan R and Chakravarty, Akhil R (2011) Remarkable photocytotoxicity in hypoxic HeLa cells by a dipyridophenazine copper(II) Schiff base thiolate. In: Journal of Inorganic Biochemistry, 105 (8). pp. 1086-1094.

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Official URL: http://dx.doi.org/10.1016/j.jinorgbio.2011.05.010

Abstract

Copper(II) complexes Cu(satp)(L)] (1-3) of a Schiff base thiolate (salicylidene-2-aminothiophenol, H(2)satP) and phenanthroline bases (L), viz. 1,10-phenanthroline (phen in 1), dipyrido3,2-d:2',3'-f]quinoxaline (dpq in 2) and dipyrido3,2-a:2',3'-c]phenazine (dppz in 3), were prepared, characterized and their anaerobic DNA photocleavage activity and hypoxic photocytotoxicity studied. The redox active complexes show the Cu(II)-Cu(I) couple near -0.5 V for 1 and near 0.0 V vs. SCE (saturated calomel electrode) for 2 and 3. The one-electron paramagnetic complexes (similar to 1.85 mu(B)) are avid DNA binders giving K(b) values within 1.0 x 10(5) - 8.0 x 10(5) M(-1). Thermal melting and viscosity data along with molecular docking calculations suggest DNA groove and/or partial intercalative binding of the complexes. The complexes show anaerobic DNA cleavage activity in red light under argon via type-I pathway, while DNA photocleavage in air proceeds via hydroxyl radical pathway. The DFT (density functional theory) calculations reveal a thyil radical pathway for the anaerobic DNA photocleavage activity and suggest the possibility of generation of a transient copper(I) species due to bond breakage between the copper and sulfur to generate the thyil radical. An oxidation of the copper(I) species is likely by oxygen in an aerobic medium or by the buffer medium in an anaerobic condition. Complex 3 exhibits significant photocytotoxicity in HeLa cells (IC(50) = 8.3(+/- 1.0) mu M) in visible light, while showing lower dark toxicity (IC(50) = 17.2(+/- 1.0) mu M). A significant reduction in the dark toxicity is observed under hypoxic cellular conditions (IC(50) = 30.0(+/- 1.0) mu M in dark), while retaining its photocytotoxicity (IC(50) = 8.0(+/- 1.0) mu M). (C) 2011 Elsevier Inc. All rights reserved.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Elsevier Science.
Keywords: Copper(II) complexes;Schiff base;Phenanthroline bases; Anaerobic DNA photocleavage;Hypoxic photocytotoxicity;HeLa cells
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)
Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited: 03 Aug 2011 06:31
Last Modified: 03 Aug 2011 06:31
URI: http://eprints.iisc.ernet.in/id/eprint/39599

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