Biological evaluation, DFT, MEP, HOMO-LUMO analysis and ensemble docking studies of Zn(II) complexes of bidentate and tetradentate Schiff base ligands as antileukemia agents

Two Schiff base ligands and some related bidentate and tetradentate Zn(II) complexes were investigated for their biological activity profiles as anticancer agents by resazurin method against two leukemia cell lines. The results clearly evidenced the importance of the tetradentate structure and the presence of the metal ion on the cytotoxicity profile of these complexes. Noteworthy, they also showed an interesting selectivity index (SI; up to 15.1 for the complex ZnL4(NO3)2 assessed on PBMC cells). The electronic behavior, stable geometries, MEP surfaces, and FMO analysis of the compounds were investigated employing density functional theory (DFT) at B3LYP level with LANL2DZ/6-311G(d,p) basic set. A comparison was made with the computational and experimental structural data of L2 and ZnL2(NO3)2 compounds. Furthermore, ensemble docking studies were undertaken on a quadruplex-duplex (Q-D) DNA model to shed light on the interactions at molecular level of the complexes with the target. In silico ADME profiling was performed using the SwissADME program, which indicated their promising therapeutic applicability.