Mode of action of tin-based anti-proliferative agents: Biological studies of organotin(IV) derivatives of fatty acids.
Some organotin(IV) carboxylates of the general formula RnSn(L)m [n=3, m=1, R=Me, Pr, Bu and Ph; n=2, m=2, R=Me, Bu and Oct; L=anion of lauric (HLA), stearic (HSA) and myristic acid (HMA)] have been synthesized and characterized by various spectroscopic studies. Tri- and diorganotin(IV) carboxylates adopt trigonal-bipyramidal and octahedral geometry around tin atom, respectively. They have been screened in vitro for anti-tumor activity against cancer cell lines of human origin, viz. MCF-7 (mammary), HEK-293 (kidney), PC-3 (prostate), HCT-15 (colon) and HepG-2 (liver). Enzyme assays viz. lipid peroxidase, glutathione peroxidase, glutathione reductase and total glutathione assay have been carried out to explore the cause of their cytotoxiciy. The results indicate that ROS (reactive oxygen species) generation may be responsible for their cytotoxicity but elevation in LDH (lactate dehydrogenase) suggests that necrosis cannot be excluded. Further, DNA (deoxyribonucleic acid) fragmentation, acridine orange and comet assay support the fact that the apoptosis is the main cause of cytotoxicity of organotin(IV) carboxylates, whereas the necrosis plays a minor role. The anti-inflammatory activity evaluation shows that the complexes possess moderate activity. Results of acute toxicity of the complexes have also been discussed.