Synthesis, in vitro antitumor activity and DNA interactions of guanidine platinum(II) complexes

Anton Legin
2010 unpublished
Recently it was discovered that platinum iminoether and amidine complexes have a high inhibitory potency on cancer cell proliferation and viability and probably possess a mechanism of action different from classic platinum drugs, as the compounds with trans-configuration are more active than cis-isomers. In this work we investigated related platinum(II) complexes with the structural element (guanidine)2PtII, prepared by nucleophilic addition of ammonia to the push-pull nitrile ligands in cis-
more » ... d trans-[PtCl2(RCN)2] (R = NMe2, NEt2, NC5H10). The neutral complexes cis-1–3 and trans-1–3 as well as the cationic complexes cis-4–6 and trans-4–6, which contain ammine instead of chloro ligands, were synthesized and characterized by Tyan M. supervised by Prof. Dr. Kukushkin V. at the Chemistry department of St. Petersburg University. In the presented work we have synthesized cationic guanidine compounds trans-[Pt(NH2Me)2{NH=C(NHMe)NR}2](Cl)2 (R = NEt2, NC5H10) (trans-7,8) by nucleophilic addition of methylamine to cyanamide platinum(II) complexes. These compounds were purified and characterized by various physical and chemical methods (elemental analysis, ESI mass spectrometry, IR, 1H NMR and 13C{1H} NMR). We have studied the biological activity of the entire set of guanidine compounds (cis-1–6 and trans-1–8), using various bioanalytical methods. Cytotoxic activity of guanidine platinum(II) complexes was determined using the colorimetric MTT assay in two human cancer cell lines: CH1 (ovarian carcinoma) and SW480 (colon cancer). IC50 values of these compounds vary within a broad range of micromolar concentrations. We could confirm the expectation that the cytotoxicity of several trans-configured complexes is higher than that of cis-congeners. The analysis showed that there is a correlation between the cytotoxic potency of the compounds and the length of the variable residue on the guanidine ligand. Moreover, cytotoxicities of the cationic complexes are mostly lower, but in some cases even comparable to those of the corres [...]
doi:10.25365/thesis.10594 fatcat:6dpf4ejwo5gnzn5tm45lo5ire4