Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3‐diaryltriazene‐substituted sulfathiazole derivatives

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, 1H‐NMR (nuclear magnetic resonance), 13C‐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 (hCA), and acetylcholinesterase (AChE), with KI 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 hCA I, 504.37 ± 57.22–1,205.36 ± 195.47 nM for hCA 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 hCA I, hCA II, and AChE, with KI 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.

Synthesis, Characterization, and Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives as α‐Glycosidase and Cholinesterase Inhibitors

“…Recently, inhibitor development and new compound synthesis studies for the enzyme have been widely carried out. In addition to treating diabetes, the α‐GLY inhibitors (α‐GLYIs) also can treat a variety of diseases, including human immunodeficiency virus, cancer, hepatitis, and heart conditions [13–16] . Additionally, α‐GLYIs have been lately found to be involved in the COVID‐19 spike blockade [17] …”

Novel benzoic acid derivatives: Synthesis and biological evaluation as multitarget acetylcholinesterase and carbonic anhydrase inhibitors

“…[ 79 ] The 3D structures of novel synthesized methylene‐aminobenzoic acid and tetrahydroisoquinolynyl‐benzoic acid derivatives ( 4a – g and 6a – g ) were sketched by ChemDraw [ 80 ] version 19.0 for Mac (PerkinElmer Inc.). They were suitably optimized for their ionization states at pH 7.4 ± 0.5 [ 81 ] with Epik [ 82 ] in the OPLS3e force field [ 83 ] using the LigPrep module [ 84 ] with default settings. The Receptor Grid Generation tool [ 85 ] was used to generate the grid for docking in the 5HF9, 6I0L, and 4E3D.…”

Synthesis and in silico studies of triazene‐substituted sulfamerazine derivatives as acetylcholinesterase and carbonic anhydrases inhibitors

“…They are one of the important groups in medicinal chemistry to design new drug candidates, as they are one of the most important linkers for many compounds and they have many roles in several applications such as biomedical applications, synthesis of natural products, and combinatorial chemistry. [ 24 ] Compounds containing a triazene structure have many activities such as antibacterial, [ 25 ] AChE inhibitory, [ 26 ] CA inhibitory, [ 27,28 ] and antitumor activities. [ 29 ] In addition, the triazene moiety is an isostere of the carbamate group that is one of the most important classes of AChE inhibitors.…”

“…However, compounds bearing a sulfonamide group and its isosteres, sulfamides and sulfamates, are the important classes of metabolic enzyme inhibitors, especially against CAs and AChE enzymes. [ 26,40 ] Furthermore, some 1,3‐diaryltriazene core‐bearing sulfonamide compounds were reported with CAs and AChE inhibitory effects. [ 26–28 ] However, 1,3‐diaryltriazene‐substituted sulfathiazole derivative compounds were reported with high hCA I, hCA II, and AChE inhibitory activities with a low‐nanomolar inhibition constant.…”

“…[ 26–28 ] However, 1,3‐diaryltriazene‐substituted sulfathiazole derivative compounds were reported with high hCA I, hCA II, and AChE inhibitory activities with a low‐nanomolar inhibition constant. [ 26 ]…”