Novel benzene sulfonamide-piperazine hybrid compounds: design, synthesis, antioxidant, enzyme inhibition activities and docking, ADME profiling studies.

Abstract

Benzene sulfonamides are an important biological substituent for several activities. In this study, hybridization of benzene sulfonamide with piperazine derivatives were investigated for their antioxidant capacity and enzyme inhibitory potencies. Six molecules were synthesized and characterized. DPPH, ABTS, FRAP, CUPRAC, chelating and phosphomolybdemum assays were applied to evaluate antioxidant capacities. Results show that compounds have high antioxidant capacity and compound 4 has the best antioxidant activity among them. Compound 4 has higher antioxidant activity than references for FRAP (IC₅₀: 0.08 mM), CUPRAC (IC₅₀: 0.21 mM) and phosphomolybdenum (IC₅₀: 0.22 mM) assays. Besides this, compound 4 has moderate DPPH and ABTS antioxidant capacity. Furthermore, enzyme inhibition activities of these molecules were investigated against AChE, BChE, tyrosinase, α-amylase and α-glucosidase enzymes. It was revealed that all compounds have good enzyme inhibitory potential except for α-amylase enzyme. The best inhibitory activities were observed for AChE with compound 5 the same value (IC₅₀: 1.003 mM), for BChE with compounds 2 and 5 the same value (IC₅₀: 1.008 mM), for tyrosinase compound 4 (IC₅₀: 1.19 mM), and for α-glucosidase with compound 3 (IC₅₀: 1.000 mM). Docking studies have been conducted with these molecules, and the results correlate well with the inhibitory assays.