Multifunctional 1,10-phenanthroline derivative and its metal complexes as an anti-Alzheimer’s agent: structure-based drug design, synthesis, characterization and pharmacological studies

Abstract

N-Heterocycles are structural constituents of pharmaceuticals based on FDA approved therapeutic agents with more than 60% of drugs containing N-heterocycles as building blocks. In the present study, a 1,10-phenanthroline derivative with metal acetates forms metal chelates of the type [M^IIL], where L = 1,10-phenanthroline derivative and M = Co(II), Zn(II), Cu(II) and Ni(II). They were characterized by analysis, spectra [IR, UV–vis, (¹H and ¹³C) NMR, mass, ESR] and magnetism as well as thermal analysis for the structural elucidation. Spectroscopic and analytical measurements confirmed an octahedral geometry for the Co(II), Zn(II), Cu(II) and Ni(II) chelates. The antimicrobial efficacy of the prepared complexes was assessed against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Aspergillus flavus, Candida albicans and Aspergillus niger. The antimycobacterial efficacy of the 1,10-phenanthroline derivative and its chelates was assessed against H₃₇Rv using Microplate Alamar Blue Assay approach and compared with a standard. The acetylcholinesterase (AChE) inhibitory effect of the ligand was examined to find the therapeutic efficiency of compound in the treatment of neurodegenerative diseases. The synthesized ligand exhibited selective inhibition against AChE and butyryl-cholinesterase with IC₅₀ values of 0.20 and 3.20 µM as compared to standards, rivastigmine and galantamine. Further, the in vitro anti-inflammatory efficiency of metal chelates was examined with the help of egg albumin method. The α-glucosidase inhibition activity was also carried out for the prepared metal complexes.

Graphical Abstract

Keywords:

• Complexes
• inhibition
• efficiency
• cytotoxicity
• antimicrobial

Acknowledgement

We thank the Head, Department of Chemistry, Manonmaniam Sundaranar University for providing the necessary facilities and the Chancellor, Noorul Islam Centre for Higher Education. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosure statement

No potential conflict of interest was reported by the authors.