title: 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 [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.
authors.affiliation: Biozentrum, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, Halle, Germany. goran.kaluderovic@chemie.uni-halle.de
authors.forename: Goran N
authors.initials: GN
authors.lastname: Kaluđerović
authors.forename: Harish
authors.initials: H
authors.lastname: Kommera
authors.forename: Evamarie
authors.initials: E
authors.lastname: Hey-Hawkins
authors.forename: Reinhard
authors.initials: R
authors.lastname: Paschke
authors.forename: Santiago
authors.initials: S
authors.lastname: Gómez-Ruiz
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D007477:Ions; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000633:toxicity*; D009947:Organotin Compounds / Q000138:chemical synthesis* / Q000633:toxicity*
chemical_list: D002264:Carboxylic Acids; D007477:Ions; D009942:Organometallic Compounds; D009947:Organotin Compounds; C030665:triphenyltin