Fluorescent Diorganotin(IV) Complexes as Anticancer Agents: Study of Cytotoxicity, Cellular Localization, and Mechanism of Cell Death

Three luminescent mixed ligand diorganotin(IV) complexes [Sn2Ph4(L)1–3(DPA)(MeOH)Cl] (where L1 = (Z)-N-((E)-3-ethoxy-2-hydroxybenzylidene)isonicotinohydrazonic acid, L2 = (Z)-N-((E)-5-bromo-2-hydroxybenzylidene)isonicotinohydrazonic acid, L3 = (Z)-N-((E)-2-hydroxy-3-methoxybenzylidene)isonicotinohydrazonic acid, and DPA = dipicolinic acid) (1–3) were synthesized and characterized physiochemically along with the single-crystal X-ray diffraction analysis of 1 and 3. Aqueous phase stabilities of the complexes were performed with UV–vis and 1H nuclear magnetic resonance, suggesting that they are stable in aqueous/biological media. The interaction of 1–3 with DNA was evaluated through analytical methods, which supported the intercalation mode of binding. Also, the interaction of complexes with bovine serum albumin was evaluated with fluorescence quenching experiments showing static quenching. In addition, the results of partition coefficients and cellular uptake suggest that the complexes are hydrophobic and can easily enter the cells. Cytotoxic potential of 1–3 was evaluated against HeLa, HT-29 (cancerous), and NIH-3T3 (normal) cell lines. Complex 2 is the most cytotoxic of the series having IC50 4.2 ± 0.7 μM against HeLa cells. Furthermore, all the complexes showed an apoptotic cell death confirmed by acridine orange/ethidium bromide, cell cycle analysis, and Annexin V-FITC/PI double staining assays. Finally, by using live cell confocal microscopy, it was found that the compounds target the mitochondria of cancer cells and raise the reactive oxygen species level