The triphenyltin(VI) complexes of NSAIDs and derivatives. Synthesis, crystal structure and antiproliferative activity. Potent anticancer agents.

The novel triphenyltin(IV) esters of flufenamic acid (1), Hflu, [Ph(3)Sn(flu)] (2), and of [2-(2,3-dichlorophenylamino)benzoic acid] (3), Hdcpa, [Ph(3)Sn(dcpa)] (4) have been structurally characterized by means of vibrational and (1)H, (13)C NMR spectroscopic studies. The crystal and molecular structures of [SnPh(3)(dcpa)(DMSO)] 4a are described. The molecular structure of 4a reveals that the Sn atom has a distorted trigonal bipyramidal coordination geometry with equatorial phenyl groups and the carboxylate and dimethylsulfoxide oxygen atoms occupying axial positions. The crystal structure of 4a is self-assembled by C-H-π and π-π stacking interactions. The in vitro cytotoxic activity of 1-4 and of the related non-steroidal anti-inflammatory drugs, NSAIDs, [2-(2,6-dimethylphenylamino)benzoic acid], Hdmpa (5), [Ph(3)Sn(dmpa)] (6), [2-(2,3-dimethylphenylamino)benzoic acid], mefenamic acid, Hmef (7) and [Ph(3)Sn(mef)] (8) has been evaluated against the cancer cell lines MCF-7, T-24, A-549 and L-929. The ligands exhibited very poor cytotoxic activity against the four cancer cell lines. Complex 6 exhibits the highest activity and selectivity against A-549 and MCF-7 cancer cell lines and complex 8 the highest activity and selectivity against T-24 cancer cell line. The cytotoxic results indicate that coupling of Hdmpa and Hmef with R(3)Sn(IV) metal center results in complexes with important biological properties and remarkable cytotoxic activity, since they display IC(50) values in a μΜ range better to that of the antitumor drug cis-platin. Complexes 6 and 8 are considered as excellent antitumor compounds and the results of this study represent the discovery of triphenyltin(IV) esters as a potential novel class of anticancer agents.