Cytotoxic activity of organotin carboxylates based on synthetic phenolic antioxidants and polycyclic bile acids

Abstract

Two series of organotin(IV) carboxylates based on phenolic antioxidants RCOOH and R(CH2)2COOH (R = 3,5-di-tert-butyl-4-hydroxyphenyl) and natural bile (cholanic) acids of formulae (RCOO)2SnMe2 (1); (RCOO)2SnBu2 (2); (R(CH2)2COO)2SnMe2 (3); (R(CH2)2COO)2SnBu2 (4); (cholate)SnPh3 (5); (deoxycholate)SnPh3 (6); (lithocholate)SnPh3 (7); (cholate)SnMe3 (8); (deoxycholate)SnMe3 (9), and (lithocholate)SnMe3 (10) were synthesized and characterized by 1H, 13C NMR, IR and elemental analysis to study their antioxidant and cytotoxic potential. Compounds 1 and 2 were found by X-ray diffraction analysis to be monomers in the solid state; moreover, the carboxyl groups are coordinated bidentately through O atoms. The distorted octahedron geometry around the Sn center in the monocrystals of 1, 2 was revealed. The antioxidant activity of compounds as radical scavengers and reducing agents was evaluated in spectrophotometrical tests with stable radical DPPH, reduction of Cu2+ (CUPRAC method) and interaction with superoxide anion radical. Cytotoxicity in vitro of compounds has been estimated on human cancer (colon cancer HCT-116, lung carcinoma A549, breast cancer MCF-7, neuroblastoma SH-SY5Y) cell lines and normal fibroblasts cells. The IC50 values varied in 0.002–100 μM range for compounds 1–4 depend on the alkyl substituents at Sn center and carboxylate ligand structure. The influence on Fe3+-induced lipid peroxidation, mitochondrial potential and mitochondrial permeability and tubulin assembly have been studied for the compounds 1 and 2. It was shown that the complexes 1 and 2 slightly depolarize the mitochondria but don’t influence the calcium-induced mitochondrial permeability transition. Organotin complexes with cholic and deoxycholic acids as ligands were revealed to induce apoptosis in A549 cells. The percentage of apoptotic cells were 27.9 and 27.1% for triphenyltin complexes with cholic and deoxycholic derivatives, respectively.