ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Molecular docking and investigation of 4-(benzylideneamino)- and 4-(benzylamino)-benzenesulfonamide derivatives as potent AChE inhibitors

Mesut Işık, Yeliz Demir, Mustafa Durgun, Cüneyt Türkeş, Adem Necip, and Şükrü Beydemir

Department of Pharmacy Services, Vocational School of Health Services, Harran University, Şanlıurfa, Turkey

E-mail: misik@harran.edu.tr

Received: 29 June 2019  Accepted: 4 November 2019

Abstract:

The discovery of acetylcholinesterase inhibitors is important for the treatment of Alzheimer’s disease (AD), known as the most common type of dementia. Due to the side effects of commonly used acetylcholinesterase inhibitors, studies for the detection of new inhibitors are increasing day by day. In this study, we investigated the effects of some sulfonamide derivatives (S1–S4 and S1i–S4i) on AChE enzymes. The best pose of the active compounds to understand the mechanism of possible inhibition in interaction of enzyme-sulfonamide derivative were performed docking studies after in vitro experimental results. ADME-related physicochemical and pharmacokinetic properties of the synthesized 4-aminobenzenesulfonamide derivatives were the compatibility with Lipinski’s rule of five. We found that the synthesized derivatives of sulfonamides show potential inhibitor properties for AChE with K_i constants in the range of 2.54 ± 0.22–299.60 ± 8.73 µM. The derivatives of sulfonamides exhibited different inhibition type. We determined that the derivatives (S1, S1i, S3, and S3i) showed a competitive inhibition effect, whereas others (S2, S2i, S4, and S4i) showed mixed-type inhibition. As a result, the sulfonamide derivatives can be used as an alternative acetylcholinesterase inhibitor due to this effect. Inhibitors with fewer side effects, are thought to be important in the treatment of AD.

Keywords: Sulfonamide derivatives; Alzheimer; AChE inhibitor; Molecular docking; Pharmacokinetic properties

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-019-00988-3

Chemical Papers 74 (5) 1395–1405 (2020)