The evaluation of potential triple enzyme inhibition and antioxidant activities of novel series 2-(benzo[d]thiazol-2-yl)phenol sulfonate derivatives

Abstract

In this study, fourteen novel 2-(benzo[d]thiazol-2-yl)phenol sulfonate compounds (5a–n) were synthesized and characterized using ¹H NMR, ¹³C NMR, and HRMS techniques. The biochemical and physicochemical properties of the sulfonate derivatives were also investigated. As a part of the study, in vitro and in silico enzyme inhibition activities of the sulfonate derivatives against acetylcholinesterase, tyrosinase, and pancreatic lipase enzymes were evaluated. According to the obtained IC₅₀ values, among the novel compounds (5a–n), compounds 5k (0.21 ± 0.06 mM) and 5i (0.22 ± 0.07 mM) were found to be the most effective acetylcholinesterase inhibitors, proving even more effective than the standard tacrine compound (0.34 ± 0.08 mM). The tyrosinase inhibition effect of the compound 5i (0.23 ± 0.07 mM) was found to be the most potent and close to the standard kojic acid (0.06 ± 0.03 mM). Also, the compound 5g (0.21 ± 0.13 mM) was found to be the most effective pancreatic lipase inhibitor, even more effective than the standard orlistat (0.26 ± 0.08 mM). According to the molecular docking studies, the binding affinity of compound 5i was found to be − 6.7 kcal/mol for the tyrosinase, − 9.1 kcal/mol for the acetylcholinesterase, and − 9.9 kcal/mol for the pancreatic lipase. The antioxidant activities of novel compounds were found to be at moderate levels in FRAP, DPPH, CUPRAC, and ABTS methods. Compound 5i (IC₅₀: 10.7 ± 1.1 mM) and compound 5j (IC₅₀: 10.9 ± 1.1 mM) exhibited effective radical scavenging antioxidant properties in DPPH methods. Finally, physicochemical properties, drug similarity, and molecular docking studies were determined using Molinspiration, PreADMET, and AutoDock Vina computational programs. Remarkably, all of in vitro, in silico, and ADMET studies had good correlations with each other and showed moderate to good inhibition properties of the novel compounds against acetylcholinesterase, tyrosinase, and pancreatic lipase enzymes.