Synthesis and evaluation of novel xanthene‐based thiazoles as potential antidiabetic agents

Abstract

A series of xanthene-based thiazoles was synthesized and characterized by different scpectroscopic methods, i.e. Proton nuclear magnetic resonance( 1 H NMR), carbon nuclear magnetic resonance ( 13 C NMR), infrared spectroscopy, carbon hydrogen nitrogen analysis, and X-ray crystallography. The inhibition potencies of 18 newly synthesized thiazole derivatives were investigated on the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase (α-Amy), and α-glycosidase (α-Gly) enzymes in accordance with their antidiabetic and anticholinesterase ability. The synthesized compounds have the highest inhibition potential against the enzymes at low nanomolar concentrations. Among the 18 newly synthesized molecules, 3b and 3p were superior to the known commercial inhibitors of the enzymes and have a much more effective inhibitory potential, with IC 50 : 2.37 and 1.07 nM for AChE, 0.98 and 0.59 nM for BChE, 56.47 and 61.34 nM for α-Gly, and 152.48 and 124.84 nM for α-Amy, respectively. Finally, the optimized 18 compounds were subjected to molecular docking to describe the interaction between thiazole derivatives and AChE, BChE, α-Amy, and α-Gly enzymes in which important interactions were monitored with amino acid residues of each target enzyme.

Synthesis, Characterization, Bioactivity Impacts of New Anthranilic Acid Hydrazones Containing Aryl Sulfonate Moiety as Fenamate Isosteres

“…It accelerates the conversion of glucose from starch and disaccharides. This enzyme break down the body‘s intake of carbs into simple molecules of glucose, which are then transported for intestinal absorption and ultimately result in hyperglycemia, an increase in blood sugar levels [1,2] . A dangerous metabolic illness called diabetes is characterized by elevated blood sugar levels.…”

Synthesis and Evaluation of Quinazolin‐4(3H)‐one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry‐Oriented Drug Design

“…It raises blood glucose levels in animals by converting starch and disaccharides into soluble monosacchar-ides like glucose. [5,6] Because of this role, α-glycosidase has been proposed as a potential therapeutic target for the treatment of type-2 diabetes in people. By slowing down the digestion of carbohydrates and subsequently the absorption of monosaccharides, inhibition of this enzyme may lower postprandial plasma glucose levels.…”

Design, Synthesis, Characterization and Biological Activities of Novel S‐(Acyloxy)butyl‐N,N‐Diethyldithiocarbamate Compounds

“…Because of this role, α-glucosidase has been proposed as a potential therapeutic target for the treatment of type-2 diabetes in people. [14,15] In the literature, it is observed that many newly synthesized organic compounds including isatin mannich bases, [16] tetrahydropyrimidine-5-carboxylates, [17] diaryl ethers, [18] 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines, [19] bromophenols, [20] cyclic thioureas, [21] sulfamides derived from βbenzylphenethylamines, [22] new amides and thiazolidineones synthesized on an acetophenone base, [23] aminomethyl and alkoxymethyl derivatives, [24] 2-hydroxyethyl substituted NHC precursors, [25] phloroglucinol derivatives, [26] novel N,N'-biscyanomethylamine and alkoxymethylamine derivatives, [27] Meta-cyanobenzyl substituted benzimidazoles, [28] novel amides of 1,1-bis-(carboxymethylthio)-1-arylethanes, [29] novel trischalcones, [30] imidazole derivatives, bis-sulfone derivatives, [31] novel benzo[b]xanthene derivatives, [32] nitrogen, phosphorus, selenium and sulfur-containing heterocyclic compounds, [33] Schiff bases containing phenol ring, [34] and piperazine derivatives [35] effectively inhibit AChE and BChE enzymes. All of these newly synthesized molecules, which inhibit both cholinergic enzymes, contain many functional groups that are important for biological activity.…”

“…It raises blood glucose levels in animals by converting starch and disaccharides into soluble monosaccharides like glucose. Because of this role, α‐glucosidase has been proposed as a potential therapeutic target for the treatment of type‐2 diabetes in people [14,15] …”