Synthesis, characterization, biological evaluation, and in silico studies of novel 1, 3‐diaryltriazene‐substituted sulfathiazole derivatives. Issue 9 (11th June 2020)

• Record Type: Journal Article
• Authors: Işık, Mesut; Akocak, Süleyman; Lolak, Nabih; Taslimi, Parham; Türkeş, Cüneyt; Gülçin, İlhami; Durgun, Mustafa; Beydemir, Şükrü
• Is Part Of: Archiv der Pharmazie. Volume 353:Issue 9(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-06-11
• Subjects: enzyme inhibition -- metabolic enzymes -- molecular docking -- sulfathiazole -- triazene; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202000102
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: In the present study, a series of eleven novel 1, 3‐diaryltriazene‐substituted sulfathiazole moieties (ST1 –11 ) was synthesized by the reaction of diazonium salt of sulfathiazole with substituted aromatic amines and their chemical structures were characterized by Fourier transform infrared, 1 H‐NMR (nuclear magnetic resonance), 13 C‐NMR, and high‐resolution mass spectroscopy methods. These synthesized novel derivatives were found to be effective inhibitor molecules for α‐glycosidase (α‐GLY), human carbonic anhydrase ( h CA), and acetylcholinesterase (AChE), with K I values in the range of 426.84 ± 58.42–708.61 ± 122.67 nM for α‐GLY, 450.37 ± 50.35–1, 094.34 ± 111.37 nM for h CA I, 504.37 ± 57.22–1, 205.36 ± 195.47 nM for h CA II, and 68.28 ± 10.26–193.74 ± 19.75 nM for AChE. Among the synthesized novel compounds, several lead compounds were investigated against the tested metabolic enzymes. More specifically, ST11 (4‐[3‐(perfluorophenyl)triaz‐1‐en‐1‐yl]‐ N ‐(thiazol‐2‐yl)benzenesulfonamide) showed a highly efficient inhibition profile against h CA I, h CA II, and AChE, with K I values of 450.37 ± 50.35, 504.37 ± 57.22, and 68.28 ± 10.26 nM, respectively. Due to its significant biological inhibitory potency, this derivative may be considered as an interesting lead compound against these enzymes. Abstract : A new series of 1, 3‐diaryltriazene‐substituted sulfathiazoles was designed, synthesized, and investigated as inhibitors of the human carbonic anhydrase ( h CA) isoforms I and II, acetylcholinesterase (AChE), and α‐glycosidase (α‐GLY). All of the derivatives showed inhibitory activity against h CA I/II, AChE, and α‐GLY, with K I values in the low nanomolar range. Molecular docking studies of these compounds were performed in this study.