TY - JOUR
T1 - Ferrocenylimine-based homoleptic metal(II) complexes
T2 - Theoretical, biocompatibility, in vitro anti-proliferative, and in silico molecular docking and pharmacokinetics studies
AU - Jayathuna, Mugamathu Ali
AU - Ahmed, Sumeer
AU - Kim, Young Guk
AU - Gajendiran, Mani
AU - Kim, Kyobum
AU - Rahiman, Aziz Kalilur
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2022/2/15
Y1 - 2022/2/15
N2 - 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.
AB - 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.
KW - Ferrocene
KW - FMOs analysis
KW - Lipinski's rule
KW - Molecular docking
KW - WST-1 assay
UR - http://www.scopus.com/inward/record.url?scp=85119908958&partnerID=8YFLogxK
U2 - 10.1016/j.molstruc.2021.131905
DO - 10.1016/j.molstruc.2021.131905
M3 - Article
AN - SCOPUS:85119908958
SN - 0022-2860
VL - 1250
JO - Journal of Molecular Structure
JF - Journal of Molecular Structure
M1 - 131905
ER -