Novel Antitumor Cisplatin
and Transplatin Derivatives
Containing 1‑Methyl-7-Azaindole: Synthesis, Characterization,
and Cellular Responses
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Abstract
The current work investigates the
effect of new bifunctional and
mononuclear Pt(II) compounds, the cis- and trans-isomers of [PtCl<sub>2</sub>(NH<sub>3</sub>)(L)] (L = 1-methyl-7-azaindole, compounds <b>1</b> and <b>2</b>, respectively), on growth and viability
of human carcinoma cells as well as their putative mechanism(s) of
cytotoxicity. The results show that substitution of 1-methyl-7-azaindole
for ammine in cisplatin or transplatin results in an increase of the
toxic efficiency, selectivity for tumor cells in cisplatin-resistant
cancer cells, and activation of the trans geometry. The differences
in the cytotoxic activities of <b>1</b> and <b>2</b> were
suggested to be due to their different DNA binding mode, different
capability to induce cell cycle perturbations, and fundamentally different
role of transcription factor p53 in their mechanism of action. Interestingly,
both isomers make it possible to detect their cellular uptake and
distribution in living cells by confocal microscopy without their
modification with an optically active tag