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

Abstract

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 [NHEt₃][P-Gly] (1), [NHEt₃][P-Ala] (2) and [NHEt₃][BTC] (3) in very high yields. The subsequent reaction of 1–3 with triphenyltin(IV) chloride (1 : 1) yielded the compounds [NHEt₃][SnPh₃Cl(P-Gly)] (4), [NHEt₃][SnPh₃Cl(P-Ala)] (5), and [NHEt₃][SnPh₃Cl(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.