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

Kerem Buran; Yiğit İnan; Abdullahi Ibrahim Uba; Gökhan Zengin

doi:10.1515/znc-2024-0062

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.

Keywords: acetylcholinesterase; antioxidant activity; benzene sulfonamides; butyrylcholine esterase; piperazine

Corresponding author: Kerem Buran, Department of Pharmaceutical Chemistry, Hamidiye Faculty of Pharmacy, University of Health Sciences, Istanbul, 34668, Türkiye, E-mail: kerem.buran@sbu.edu.tr

All authors contributed equally to this work.

Acknowledgments

This study was supported by the University of Health Sciences, unit of scientific research project (BAP, project no.: 2020/040).

Research ethics: Not applicable.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: University of Health Sciences, unit of scientific research project (BAP) (project no.: 2020/040).
Data availability: Not applicable

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/ZNC-2024-0062).

Received: 2024-03-23

Accepted: 2024-06-09

Published Online: 2024-06-24

Published in Print: 2024-11-26

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Supplementary Material