Bis(azo-mine) based transition metal complexes: synthesis, spectroscopy, DNA binding, docking studies, and α-glucosidase inhibition activity

Abstract

In this work, two new mononuclear transition metal complexes: [M(L)], (M: Zn(II) for 2a, Mn(II) for 2b), with H2L (2,2′-{propane-1,3-diylbis[nitrilo(E)methylylidene]}bis{4-[(E)-phenyldiazenyl]phenol}, as the primary ligand (2) and a hetero-binuclear complex (3a): [Zn(L)Cu(phen) (ClO4)2], with the primary mononuclear Zn(II) complex, 2a, Cu(ClO4)2.6H2O and 1,10-phenanthroline as bidentate co-ligand(s) have been synthesized and characterized by using elemental analysis, FTIR, UV–Vis, NMR, H-ESI, and MALDI-TOF mass spectrometry. The biological activity assays of the compounds containing DNA interaction, antiproliferation, antimicrobial and antidiabetic activity tests, and molecular docking studies were performed. Complex 3a has the highest Kb value, 7.00 × 105, and the most effective nuclease activity and computationally exhibits strong and versatile partial-intercalation type interactions with DNA. The anti-proliferation activities of all compounds were evaluated against human cancer cells. Complex 2b showed the highest anticancer activity (IC50 = 22.46 ± 1.43 μg/mL) against HT-29 cells and (IC50 = 39.79 ± 6.71 μg/mL) against DU-145 cells. All of the compounds showed an inhibition effect on Gram (+) bacteria Staphylococcus aureus and Bacillus subtilis. Complex 3a shows the most effective antidiabetic activity with the lowest IC50 value (7.64 ± 0.13) and inhibits the α-glucosidase enzyme in a non-competitive manner. Enzyme docking studies also revealed that complex 3a exhibited the most effective and strongest binding to the α-glucosidase enzyme. Consequently, due to their effective DNA binding, nuclease, antidiabetic, antimicrobial, and anticancer activities, complexes 2b and 3a may be favorable candidates for further applications in medical therapy.