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

• Published in: Journal of inorganic biochemistry Vol. 105; no. 2; pp. 195 - 201
• Main Authors: Dokorou, Vaso, Primikiri, Alexandra, Kovala-Demertzi, Dimitra
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2011
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Cell Line, Tumor; Cell Proliferation - drug effects; Complexes; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystal structure; Crystallography, X-Ray; Drug Design; Drug Screening Assays, Antitumor; Esters; Flufenamic Acid - chemistry; Humans; Mefenamic Acid - chemistry; Mice; Molecular Conformation; Organotin Compounds - chemistry; Spectral studies; Structure-Activity Relationship; Triphenyltin(IV); Spectral studies; Antiproliferative activity; Complexes; Triphenyltin(IV); Crystal structure
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2010.10.008

The novel triphenyltin(IV) esters of flufenamic acid (1), Hflu, [Ph3Sn(flu)] (2), and of [2-(2,3-dichlorophenylamino)benzoic acid] (3), Hdcpa, [Ph3Sn(dcpa)] (4) have been structurally characterized by means of vibrational and 1H, 13C NMR spectroscopic studies. The crystal and molecular structures of [SnPh3(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), [Ph3Sn(dmpa)] (6), [2-(2,3-dimethylphenylamino)benzoic acid], mefenamic acid, Hmef (7) and [Ph3Sn(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 R3Sn(IV) metal center results in complexes with important biological properties and remarkable cytotoxic activity, since they display IC50 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.
The novel triphenyltin(IV)esters of flufenamic acid (1), Hflu, [Ph3Sn(flu)] (2), and of [2-(2,3-dichlorophenylamino)benzoic acid] (3), Hdcpa, [Ph3Sn(dcpa)] (4) have been characterized by spectroscopic studies. The crystal and molecular structures of [SnPh3(dcpa)(dmso)] is described. The in vitro cytotoxic activity of 1–4 and of the related NSAIDs has been evaluated against cancer cell lines MCF-7, T-24, A-549 and L-929. The results of this study represent the discovery of triphenyltin(IV)esters as a potential novel class of anticancer agents. [Display omitted]