Syntheses, structural snapshots, solution redox properties, and cytotoxic performances of designated ferrocene scaffolds appended with organostannyl(IV) benzoates en route for human hepatic carcinoma

Although several strategies have been established to circumvent the limitations of platinum-based chemotherapy, the basic problems still persist. For this purpose, the new series of heterobimetallic formulations [FcLnSnPh3] (1, 3, and 9)], [FcLnSnBu3]n(2, 4 and 8), [FcL3SnCy3] (10), and [FcL3SnR3(MeOH)] (R = Me (5), Et (6), or Pr (7)), where FcLn(n = 1-3) refers to the isomeric 2-/3-/4-ferrocenylbenzoates, was synthesized which can target cancer cells and successively support functional iron deficiencies during chemotherapy. Compounds 1-10 have been characterized by elemental analysis, and their spectroscopic properties were investigated using IR, NMR, electronic, and fluorescence techniques. The molecular structures of metallo proligands FcL1H and FcL3H and the six heterobimetallic compounds 2, 3, 5-7, and 10 have been determined by X-ray crystallography. The redox properties of FcLnH and their compounds 1-10 were also investigated by cyclic voltammetry. In vitro cytotoxic activities of compounds 1-4, 8, and 9 were assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against human hepatic carcinoma (HepG2) cells, with IC50values revealing high activity better than that of doxorubicin. More importantly, compound 2 demonstrated maximum inhibition in HepG2 cells (IC50= 0.10 μM) among other studied cell lines of human origin, e.g. embryonic kidney (HEK-293T), breast (MDA-MB-231), and lung (A-549) cancer cells, with negligible effect on human peripheral blood mononuclear cells (PBMC). Compound 2 effectively inhibited cell viability, and the apoptosis proceeded via activation of caspases and cleavages of caspase-dependent proteins, as revealed from a PARP cleavage assay. Membrane microviscosity results point toward changes in fluidity that are sufficient to stop biological activities mediated by growth factors.