Synthesis, characterization, and biophysical and chemical properties of benzo[b]thiophene derivatives and their metal complexes†

Abstract

New effective antioxidant, antimicrobial, anti-inflammatory, enzyme-inhibiting, and cytotoxic agents with novel modes of action are urgently needed due to the continued emergence of various diseases. Four novel Schiff base ligands containing a benzo[b]thiophene moiety were synthesized, leading to the development of a versatile class of Ni(II) and Mn(II) complexes, which were screened for their biological applications. The Schiff base ligands were characterized quantitatively using standard spectroscopic techniques such as elemental analysis, UV-vis spectroscopy, FT-IR spectroscopy, LC-MS, ¹H NMR spectroscopy and ¹³C NMR spectroscopy, while the metal complexes were characterized using UV-vis spectroscopy, FT-IR spectroscopy, CHNS analysis, ICP-MS, thermal analysis (TG and DTG), molar conductance and magnetic susceptibility measurements. The coordination structure of the complexes was found to be octahedral geometry, with Ni(II) and Mn(II) metal ions coordinated to a nitrogen atom of azomethine group, a benzo[b]thiophene ring, an oxygen atom of the phenolic group and an acetate derivative. Among the synthesized compounds, the biological properties of the complexes were found to be more potent than those of Schiff base ligands. Their antioxidant, antibacterial, anti-inflammatory, enzyme inhibitory, and cytotoxic activities were assessed. The antioxidant activity of the developed compounds was tested using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay in methanol and buffered methanol solutions. All the Schiff base ligands and their Ni(II)/Mn(II) complexes exhibited antioxidant activities comparable to the standards (BHT and ascorbic acid). The in vitro antibacterial activity of the synthesized compounds was evaluated against Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Bacillus subtilis (B. subtilis), and Staphylococcus aureus (S. aureus) and their antifungal activity using fungal strains, such as Aspergillus niger (A. niger), and Candida albicans (C. albicans). These activities were observed using the agar disc diffusion method, with ciprofloxacin and nystatin as the reference drugs. The HRBC membrane stabilization method was applied to measure anti-inflammatory activity, and one of the Mn(II) compounds showed moderate anti-inflammatory activity, which was compared with the standard drug diclofenac. Enzyme inhibition studies were conducted on benzo[b]thiophene-derived Schiff base ligands and their complexes with the enzyme α-amylase, using acarbose as the standard. The Ni(II) complexes exhibited the best enzyme inhibition value (K_i). To assess the cytotoxic behavior of the synthesized compounds and determine cell viability, two methods were used: the trypan blue exclusion method for cancer cell lines, such as DLA cells and HepG2 cells, and the MTT assay for human cells, such as H9c2 cells. Encouragingly, most of the compounds were generally non-toxic to the human cells (H9c2).