Mechanism of Cytotoxicity of Copper(I) Complexes of 1,2-Bis(diphenylphosphino)ethane

Sanghamitra, Nusrat J and Phatak, Pornima and Das, Sanjeev and Samuelson, Ashoka G and Somasundaram, Kumaravel (2005) Mechanism of Cytotoxicity of Copper(I) Complexes of 1,2-Bis(diphenylphosphino)ethane. In: Journal of Medicinal Chemistry, 48 (4). pp. 977-985.

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Abstract

The cytotoxic properties of arylphosphines are regulated by metals. We have synthesized a series of copper(I) complexes of 1,2-bis(diphenylphosphino)ethane (DPPE) and tested their in vitro cytotoxicity in a human lung carcinoma cell line H460. One of the complexes $[Cu_2(DPPE)_3(CH_3CN)_2](ClO_4)_2 (C1)$, showed maximum cytotoxicity comparable to that of adriamycin. Treatment of cells with C1 caused DNA damage in vitro and activated the p53 pathway. Flow cytometry revealed that growth inhibition by C1 was due to a combination of cell cycle arrest and apoptosis. Simultaneous addition of C1 and adriamycin increased the cytotoxicity of either compound, suggesting the potential use of adriamycin in combination with C1. DNA binding and simulation studies suggest that adriamycin binds to DNA synergistically in the presence of C1. Thus, we have identified C1, a copper(I) complex of DPPE, as a potential chemotherapeutic drug for further testing, which could be used either alone or in combination with other chemotherapeutic drugs.

Item Type:	Journal Article
Publication:	Journal of Medicinal Chemistry
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society.
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	27 Apr 2005
Last Modified:	20 Jan 2012 06:37
URI:	http://eprints.iisc.ac.in/id/eprint/2887

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