Synthesis, characterization, molecular docking and network pharmacology of bioactive metallic sulfonamide-isatin ligands against promising drug targets

Abstract

A series of sulfonamide and isatin based Schiff bases, (S1) and (S2), and their metal (Co2+, Ni2+, Cu2+ and Zn2+) complexes (1)-(8) were synthesized and characterized by spectroscopic (UV, IR, MS, 1H and 13C-NMR), elemental, magnetic and physical techniques. The non-electrolytic character of Co2+, Ni2+, and Zn2+ compounds and electrolytic nature of Cu2+ was established by their conductance studies. The energies of Frontier Molecular Orbitals (FMOs) were also used to explore various global and quantum chemical qualities. To find the activity and molecular targets in curing Alzheimer's Disease (AD) and Carbonic Anhydrase II (CA-II) inhibition, Network Pharmacology modeling was used. The prospective targets were predicted using the Swiss Target PredictionR online facility. The Gene CardsR database has been used to find genes linked to AD and CA-II. We also conducted Gene OntologyR (GO) analysis on the intersecting genes targets on active targets of synthesized compounds by DAVID (Database for Annotation, Visualization and Integrated Discovery) Bioinformatics Services using the CytoscapeR program. The in vitro enzyme inhibition assays were done against protease, amylase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) while their antimicrobial studies were performed against pathogenic bacterial and fungal species. The antioxidant values, evaluated as 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing assay power (FRAP) (%) ranged between 51.0±0.11-68.1±0.11% with IC50 ranging 146.84-196.08 µL/mol.