Synthesis, characterization, in vitro cytotoxic activity and molecular docking of dinuclear gold(I) complexes with terephthalaldehyde bis(thiosemicarbazones)

Abstract Four new bis(thiosemicarbazones) were synthesized and, by reaction with AuI, four dinuclear gold(I) complexes were obtained. Cytotoxic activity of both the ligands and the complexes against NCI-H460 (lung), A2780 and A2780cisR (ovarian) cancer cell lines and normal renal LLC-PK1 cells has been evaluated. The results indicate that the ligands do not show antiproliferative activity in the cell lines evaluated and the NCI-H460 line is only sensitive to the complex bearing cyclohexyl substituents. On the other hand, the four complexes display high cytotoxic activity towards A2780 and A2780 cisR and the complex with thiosemicarbazide could circumvent resistance to cisplatin. By contrast, none of the complexes show significant inhibition against the normal renal cell line LLC-PK1. Docking studies with carboxamide ribonucleotide formyltransferase (AICARFT) and cyclin-dependent kinases (CDK2) for lung and ovarian cancer, respectively, show that the best binding affinity corresponds to complex 4, which is in agreement with the in vitro cytotoxicity.