Trans- and cis-2-phenylindole platinum(II) complexes as cytotoxic agents against human breast adenocarcinoma cell lines

The synthesis and characterization of the new 2-phenylindole derivative: C8H3N-2-C6H5-3NOMe-5OMe (3c) and the trans- and cis-isomers of [Pt(3c)Cl-2(DMSO)] complexes (4c and 5c, respectively) are described. The crystal structures of 4c center dot CH2Cl2 and 5c confirm: (a) the existence of a Pt-N-indole bond, (b) the relative arrangement of the Cl- ligands [trans- (in 4c) or cis- (in 5c)] and (c) the anti-(E) configuration of the oxime. The cytotoxic assessment of C8H3N-2-(C6H4-4'R-1)-3NOMe-5R(2) [with R-1 = R-2 = H (3a); R-1 = Cl, R-2 = H (3b) and R-1 = H, R-2 = OMe (3c)] and the geometrical isomers of [Pt(L)Cl-2(DMSO)] with L = 3a-3c [trans- (4a-4c) and cis- (5a-5c), respectively] against human breast adenocarcinoma cell lines (MDA-MB231 and MCF-7) is also reported and reveals that all the platinum(II) complexes (except 4a) are more cytotoxic than cisplatin in front of the MCF7 cell line. Electrophoretic DNA migration studies of the synthesized compounds in the absence and in the presence of topoisomerase-1 have been performed, in order to get further insights into their mechanism of action. (c) 2013 Elsevier B.V. All rights reserved.