Synthesis and biological applications of ionic triphenyltin(IV) chloride carboxylate complexes with exceptionally high cytotoxicity.

The reaction of N-phthaloylglycine (P-GlyH), N-phthaloyl-l-alanine (P-AlaH), and 1,2,4-benzenetricarboxylic 1,2-anhydride (BTCH) with triethylamine led to the formation of the corresponding ammonium salts [NHEt(3)][P-Gly] (1), [NHEt(3)][P-Ala] (2) and [NHEt(3)][BTC] (3) in very high yields. The subsequent reaction of 1-3 with triphenyltin(iv) chloride (1 : 1) yielded the compounds [NHEt(3)][SnPh(3)Cl(P-Gly)] (4), [NHEt(3)][SnPh(3)Cl(P-Ala)] (5), and [NHEt(3)][SnPh(3)Cl(BTC)] (6), respectively. The molecular structure of 4 was determined by X-ray diffraction studies. The cytotoxic activity of the ammonium salts (1-3) and the triphenyltin(iv) chloride derivatives (4-6) were tested against human tumor cell lines from five different histogenic origins: 8505C (anaplastic thyroid cancer), A253 (head and neck cancer), A549 (lung carcinoma), A2780 (ovarian cancer) and DLD-1 (colon cancer). Triphenyltin(iv) chloride derivatives (4-6) show very high activity against these cell lines while the ammonium salts of the corresponding carboxylic acids (1-3) are totally inactive. The most active compound is 4 which is 50 times more active than cisplatin. Compound 4 is found to induce apoptosis via extrinsic pathways on DLD-1 cell lines, probably by accumulation of caspases 2, 3 and 8. Furthermore, compound 4 seems to cause disturbances in G1 and G2/M phases in cell cycle of DLD-1 cell line.