Design, spectral characterization, anti-tumor and anti-inflammatory activity of triorganotin(IV) hydroxycarboxylates, apoptosis inducers: In vitro assessment of induction of apoptosis by enzyme, DNA-fragmentation, acridine orange and comet assays

• Triorganotin-based new anti-cancer agents have been synthesized and characterized.
• Enzyme assays indicate that the reactive oxygen species generated in cancer cells.
• DNA fragmentation, acridine orange and comet assays support apoptosis.
• They exhibit low toxicity and good anti-inflammatory activity.

Interaction of triorganotin(IV) chlorides with sodium salt of hydroxycarboxylic acids results in the formation of triorganotin(IV) hydroxycarboxylates, R3Sn(L) [R = Me, n-Bu and Ph; L = anion of glucuronic (HGlu), gallic (HGal) and mandelic (HMal) acid]. They exhibit trigonal–bipyramidal geometry which is well supported by elemental analysis, IR, 1H, 13C, 119Sn NMR and ESI-MS spectral data. Triorganotin(IV) hydroxycarboxylates have been screened in vitro against five cancer cell lines of human origin viz. MCF-7, HEK-293, PC-3, HCT-15 and HepG-2. Title complexes are found to be cytotoxic to mildly cytotoxic, and exhibited IC50 values in the range 4–30 μg/mL. The results of enzyme assays viz. glutathione reductase, glutathione peroxidase, total glutathione content and lipid peroxidase assay on MCF-7 cells indicate that the reactive oxygen species generated in the cancer cells by triorganotin(IV) hydroxycarboxylates is responsible for cell death. Marginal increase of lactate dehydrogenase suggests that necrosis is also occurring to a small extent. DNA (deoxyribonucleic acid) fragmentation assay, acridine orange assay and comet assay clearly support that the cell death is mainly due to apoptosis. The results obtained for the in vivo anti-inflammatory activity (% inhibition) and toxicity (LD50 in mg/kg) suggested that the complexes have low toxicity and good anti-inflammatory activity.

Triorganotin(IV) hydroxycarboxylates, R3Sn(L) [R = Me, n-Bu and Ph; L = anion of glucuronic (HGlu), gallic (HGal) and mandelic (HMal) acid] exhibit trigonal–bipyramidal geometry and are found to be cytotoxic to mildly cytotoxic. They are apoptosis inducers as supported by DNA fragmentation, enzymes, acridine orange and comet assays. They also exhibit good anti-inflammatory activity in vivo and have low toxicity.Figure optionsDownload as PowerPoint slide