Synthesis and investigation of new indole-containing vinyl sulfide derivatives: In silico and in vitro studies for potential therapeutic applications

Indoles featuring organosulfur compounds serve as privileged structural scaffolds in various biologically active compounds. This study investigates the biological properties of five synthetic sulphenyl vinyl indoles (3 a-e) using both in silico and in vitro methods. Computational analyses employing Swiss ADME and Molinspiration software reveal the remarkable inhibitory activity of compound 3 d against proteases and kinases (scores of 0.18 and 0.06, respectively). Furthermore, it demonstrates the ability to modulate ionic and G protein-coupled receptors (scores: -0.06 and 0.31, respectively) and serves as a ligand for nuclear receptors (score 0.15). In vitro investigations highlight the compounds' efficacy in countering ABTS⁺ radical attacks and reducing lipid peroxidation levels. Particularly noteworthy is the superior efficacy of compounds 3 a, 3 b, and 3 e in DPPH (EC₅₀ 3 a: 268.5 μM) and TEAC assays (EC₅₀ 3 a: 49.9 μM; EC₅₀ 3 b: 133.4 μM, and EC₅₀ 3 e: 84.9 μM), as well as TBARS levels. Compound 3 c significantly reduces acetylcholinesterase activity, positioning itself as a noteworthy Enzyme inhibitor. This study emphasizes the versatile biological potential of synthetic indole derivatives, suggesting their applicability for therapeutic purposes.

Anticholinesterase; Antioxidant; Computational analysis; Indole-derivatives; Vinyl-Sulfide.