Pro-Apoptotic Organometallic Sn(IV) Bis-Organosilane Benzoate Complexes with Sustained Reduction in Cell Viability Under Resistance-like Conditions in Colorectal Cancer Cells

This work reports the synthesis, characterization and in vitro evaluation of three organometallic triorganotin(IV) complexes bearing a dicarbamido-bis-organosilane benzoate ligand as potential anticancer agents against colorectal cancer cells. The complexes, Sn(IV)-biSi-1, Sn(IV)-biSi-2 and Sn(IV)-biSi-3, differ in the alkyl groups directly bound to the Sn(IV) center (methyl, n-propyl and isopropyl, respectively). Their structures were confirmed by 1H, 13C and 119Sn NMR spectroscopy, FTIR and ESI-MS, supporting monodentate carboxylate coordination and a solvent-dependent Sn(IV) coordination environment. Biological assays in HCT116 cells showed that the final bis-organosilane complexes were markedly more active than their aminobenzoate intermediates and, under several conditions, more effective than cisplatin. Sn(IV)-biSi-2 and Sn(IV)-biSi-3 reduced cell viability to approximately 30% at 0.5 μM after 5 days and to about 11% and 7%, respectively, at 12.5 μM. In repeated-treatment assays, these complexes maintained antiproliferative activity more efficiently than cisplatin, limiting resistance-like cell recovery. Western blot analysis revealed increased γ-H2AX, p53, cleaved caspase-3 and cleaved PARP, indicating DNA damage-associated apoptotic signaling. Overall, these results identify bis-organosilane triorganotin(IV) benzoates, especially Sn(IV)-biSi-2 and Sn(IV)-biSi-3, as promising metal-based anticancer candidates that sustain antiproliferative activity after repeated exposure in colorectal cancer cells and may contribute to strategies aimed at therapy-resistant colorectal tumors.