A trans-dichloridoplatinum(II) complex of a monodentate nitrogen mustard: Synthesis, stability and cytotoxicity studies.

A trans-dichloridoplatinum(II) complex of a monodentate nitrogen mustard: Synthesis, stability and cytotoxicity studies. J Inorg Biochem. 2019 Dec 28;204:110982 Authors: Karmakar S, Chatterjee S, Purkait K, Mukherjee A Abstract A trans-dichloridoplatinum(II) complex, trans-[PtIICl2(L)(DMSO)] (1) of a monodentate nitrogen mustard, bis(2-chloroethyl)amine (L), was synthesized by the reaction of cis-[PtIICl2(DMSO)2] &L.HCl in presence of Et3N. 1 was characterised by NMR, FT-IR and elemental analysis. L is unstable in aqueous solution while 1 displayed moderate stability. In aqueous buffer solution of pD 7.4, 1 starts to loose L slowly upon dissolution and even after 48 h there is still intact/aquated complex present in solution. 1 interacts with the model nucleobase 9-ethyl guanine. The ligand L was non-toxic against MCF-7, A549, HepG2 & MIA PaCa-2 up to 200 μM. In contrast, the Pt(II) complex 1 showed an excellent IC50 (ca. 600 nM) against MIA PaCa-2 and also displayed good IC50 value (3-7 μM) against the other cancer cell lines probed. The in vitro cytotoxicity of 1 is better than cisplatin against each of the treated cancer cell lines and it is not affected by hypoxia as per the in vitro studies. Complex 1 displays higher cellular accumulation than cisplatin and arrests the cell cycle in both S & G2/M phase inducing apoptotic cell death. The G2/M phase arrest is dominant at higher concentrations. The depolarisation ...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research