Study of the cytotoxic activity of di and triphenyltin(IV) carboxylate complexes

Santiago Gómez-Ruiz, Goran N. Kaluđerović, Sanjiv Prashar, Evamarie Hey-Hawkins, Aleksandra Erić, Željko Žižak, Zorica D. Juranić

The reaction of 3-methoxyphenylacetic acid (3-MPAH), 4-methoxyphenylacetic acid (4-MPAH), 2,5-dimethyl-3-furoic acid (DMFUH) or 1,4-benzodioxane-6-carboxylic acid (BZDOH) with triphenyltin(IV) chloride (1:1) or diphenyltin(IV) dichloride (2:1) in the presence of triethylamine yielded the compounds [SnPh3(3-MPA)] (1), [SnPh3(4-MPA)] (2), [SnPh3(DMFU)] (3), [SnPh3(BZDO)] (4), [SnPh2(3-MPA)2] (5), [SnPh2(4-MPA)2] (6), [SnPh2(DMFU)2] (7) and [SnPh2(BZDO)2] (8), respectively. The tetranuclear complex [{Me2(DMFU)SnOSn(DMFU)Me2}2] (9) was prepared by the reaction of dimethyltin(IV) oxide and 2,5-dimethyl-3-furoic acid (DMFUH). The molecular structures of 3, 4 and 9, were determined by X-ray diffraction studies. The cytotoxic activity of the carboxylic acids (3-MPAH, 4-MPAH, BZDOH and DMFUH) and di (5-8) and triphenyltin(IV) complexes (2-4) was tested against tumor cell lines human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x and normal immunocompetent cells, peripheral blood mononuclear cells PBMC. Triphenyltin(IV) complexes show higher activities than the diphenyltin(IV) derivatives. The most active compound is [SnPh3(DMFU)] (3) with IC50 value of 0.15+/-0.01, 0.051+/-0.004, 0.074+/-0.004, 0.20+/-0.01, 0.15+/-0.02 on HeLa, K562, Fem-x, rested and stimulated PBMC, respectively, while the most selective are [SnPh2(3-MPA)2] (5), [SnPh(2)(DMFU)2] (7) and [SnPh((BZDO)2] (8). Compounds 3, 5, 7 and 8 present higher activities than cisplatin in all the tested cells and relative high selectivity especially on K562 cells.