Ferrocenylimine-based homoleptic metal(II) complexes: Theoretical, biocompatibility, in vitro anti-proliferative, and in silico molecular docking and pharmacokinetics studies

Abstract

Three new ferrocenylimine-based homoleptic metal(II) complexes with general formula [M(L)2(H2O)2](ClO4)2 (1‒3), where L = trans-4-(ferrocenylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, and M = Ni2+, Cu2+ and Zn2+ have been synthesized and characterized by spectroscopic methods. The spectral and theoretical studies revealed the distorted octahedral (Oh) geometry for the synthesized complexes with the involvement of azomethine nitrogen, carbonyl oxygen and oxygen atom of water molecules in coordination to metal(II) ion. The UV–vis and cyclic voltammetric techniques were employed to understand the reduction behaviour of copper(II) complex (2) in ascorbic acid. The in vitro biocompatibility studies show the risk-free nature of complexes to NHDF (normal human dermal fibroblast) cell line up to the concentration level of 100 µg/mL. In vitro anti-proliferative activity was investigated on two human cancerous MCF-7 (breast adenocarcinoma) and HepG2 (hepatoma), and one non-cancerous NHDF (normal human dermal fibroblast) cell lines by MTT reduction assay. The complexes showed higher anti-proliferative activity and biocompatibility without showing any toxicity towards normal cell lines. The docking studies indicated H-bonding, π-pair and hydrophobic interactions between complexes and protein molecules (VEGF, EGF and CEA receptors). In addition, the pharmacokinetics properties were analyzed using Lipinski's ʹrule of fiveʹ and the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties, which predicted the drug-likeness and bio-activity of the synthesized complexes.