In vitro cytotoxicity evaluation of organotin(IV) complexes derived from bisphosphoramide ligand: DNA binding and molecular docking studies

Considering the valuable position of organotins and the biotic role of phosphorus compounds in biological processes, in this research work, we investigated and introduced a new class of anticancer candidates based on organotin(IV) complexes derived from bisphosphoramide ligands. Four selected complexes were prepared from the reaction of SnMe2Cl2 (C1), SnBu3Cl (C2), SnPh2Cl2 (C3), and SnPh3Cl (C4) metal salts with piperazine-1,4-diylbis(diphenylphosphine oxide) ligand (LP). The newly synthesized complexes were characterized using spectroscopic techniques. Single crystal of C1 structure was determined by X-ray crystallography. Binding po-tentials of compounds to DNA were also explored using electron absorption titration and competitive fluores-cence quenching techniques, which indicated that complexes and CT-DNA strongly interacted. Cytotoxicity assay of compounds against triple-negative human breast cancer (MDA-MB-231) cells proved that three complexes C2, C3, and C4 had a very considerable impact on the reduced viability of cancer cells and among them, C4 revealed the maximum anticancer activity (IC50 = 0.35 +/- 1.18 mu g/mL, 0.28 mu M) in comparison to reference cisplatin drug (IC50 = 19 mu M). Furthermore, the analysis and comparison of the orientations and reactive sites of the com-pounds using molecular docking simulation, pharmacophore, and NCI studies further confirmed the significant effects of the type and number of aryl and alkyl substituents on the biological activities.

Automated summary

This research work investigated and introduced a new class of anticancer candidates based on organotin(IV) complexes derived from bisphosphoramide ligands. The synthesized complexes showed strong interaction with CT-DNA and exhibited considerable anticancer activity against triple-negative human breast cancer cells. The analysis further confirmed the significant effects of the type and number of substituents on the biological activities.