Synthesis, characterization, inhibition effects, and molecular docking studies as acetylcholinesterase, α-glycosidase, and carbonic anhydrase inhibitors of novel benzenesulfonamides incorporating 1,3,5-triazine structural motifs

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 (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, biological evaluation, and in silico studies of novel 1,3-diaryltriazene-substituted sulfathiazole derivatives.

A series of six N-carbamimidoyl-4-(3-substituted phenylureido)benzenesulfonamide derivatives were synthesized by reaction of sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects of the novel ureido-substituted sulfaguanidine derivatives were investigated by spectrophotometric methods for α-glycosidase (α-GLY), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes associated with diabetes mellitus (DM) and Alzheimer's disease (AD). N-Carbamimidoyl-4-{[(3,4-dichlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2f) showed AChE and BChE inhibitory effects, with KI values of 515.98±45.03 nM and 598.47±59.18 nM, respectively, while N-carbamimidoyl-4-{[(3-chlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2e) showed strong α-GLY inhibitory effect, with KI values of 103.94±13.06 nM. The antidiabetic effects of the novel synthesized compounds are higher than their anti-Alzheimer's effects, because the inhibition effect of the compounds on the α-GLY with diabetic enzyme is greater than the effect on esterase enzymes. Indeed, inhibition of the metabolic enzymes is important for the treatment of DM and AD.

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

Discovery of new ureido benzenesulfonamides incorporating 1,3,5-triazine moieties as carbonic anhydrase I, II, IX and XII inhibitors.

1,3,5-Triazine and its derivatives have been the epicenter of chemotherapeutic molecules due to their effective biological activities, such as antibacterial, fungicidal, antimalarial, anticancer, antiviral, antimicrobial, anti-inflammatory, antiamoebic, and antitubercular activities. The present review represents a summarized report of the crucial biological activities possessed by substituted 1,3,5-triazine derivatives, with special attention to the most potent compounds.

1,3,5-Triazine: A versatile pharmacophore with diverse biological activities.

A series of 16 novel benzenesulfonamides incorporating 1,3,5-triazine moieties substituted with aromatic amines, dimethylamine, morpholine and piperidine were investigated. These compounds were ass...

Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile.

1,3-diaryltriazenes are one of the most useful and important linkers for many pharmaceutical applications. Therefore, in the current work, a series of 1,3-diaryltriazene sulfonamides 4(a-k) were synthesized by reacting diazonium salt of sulfanilamide and substituted aromatic amine derivatives 3(a-k) . The obtained compounds were investigated for antioxidant properties by using different methods such as a DPPH radical scavenging assay, ABTS radical decolarization, cupric reducing antioxidant capacity (CUPRAC) and metal chelating methods. The cholinesterase inhibition activities (acetylcholinesterase and butyrylcholinesterase) of synthesized compounds were also tested. In general, compounds showed weak antioxidant activity, except compounds 4d (IC 50 =114.89 for DPPH activity), 4i (IC 50 =25.31 for ABTS activity), 4a (IC 50 = 86.33 for metal chelating activity), and 4k (absorbance value 1.229 µM for CUPRAC). Some of the compounds showed great % inhibition against both acetylcholinesterase and butyrylcholinesterase with % inhibition values ranging from 11.54 to 93.67 and 62.24 to 98.47, respectively.

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Design, synthesis and biological evaluation of 1,3-diaryltriazene-substituted sulfonamides as antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitors

In this work, a series of histamine Schiff bases H(1-20) were synthesized by reacting histamine and substituted aldehydes A(1-20) . The compounds were assayed for antioxidant properties by using different bioanalytical methods such as DPPH free radical scavenging assay, ABTS cation radical decolarization, cupric reducing antioxidant capacity (CUPRAC) and metal chelating methods. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition profiles were also assessed. In general, the synthesized compounds showed weak antioxidant activity against all tested methods, but some of the compounds showed great inhibition potency against AChE and BChE enzymes. Specifically, compound H9 showed effective inhibition potency against both enzymes with % inhibition of 97.03 and 93.64, respectively.

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Antioxidant, acetylcholinesterase and butyrylcholinesterase inhibition profiles of histamine Schiff bases

In Silico Studies and DNA Cleavage, Antioxidant, Acetylcholinesterase, and Butyrylcholinesterase Activity Evaluation of Bis-Histamine Schiff Bases and Bis-Spinaceamine Substituted Derivatives

Schiff base compounds (((1Z,1′Z)-(((ethane-1,2-diylbis(sulfanediyl))bis(2,1-phenylene))bis(azanylylidene)) bis(methanylylidene)) bis(4,1-phenylene))diboronic acid (1), 1,1′-((1Z,1′Z)-([1,1′-biphenyl]-4,4′-diylbis( azanylylidene)) bis(methanylylidene)) bis(naphthalen-2-ol) (2), 4,4′-((1Z,1′Z)-([1,1′-biphenyl]-4,4′-diylbis(azanylylidene)) bis(methanylylidene)) bis(2-methoxy phenol) (3), (N4Z,N4′Z)-N4,N4′-bis(4-(dimethyl amino) benzylidene)-[1,1′-biphenyl]-4,4′-diamine (4), (E)-2-((2-hydroxybenzylidene)amino) terephthalic acid (5), and (E)-2-(((2-hydroxynaphthalen-1-yl)methylene)amino)terephthalic acid (6) have been synthesized. The structural identification was confirmed by spectroscopic techniques. The antiproliferative, antiradical, and enzyme activities were investigated in biological experimen0ts. The obtained results showed that Schiff base compounds 1 – 6 exhibited meaningful features in various biological tests. A comparison of compound 1 (containing boron atom in the structure) to compounds 2 – 6 shows that the inclusion of boron in the Schiff base determines whether this would increase or not the efficiency in biological experiments. Hereby, compound 1 exhibited significantly different results in all applications.

Muhammed Tuneg

Papers

Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile.

Design, synthesis and biological evaluation of 1,3-diaryltriazene-substituted sulfonamides as antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitors

Antioxidant, acetylcholinesterase and butyrylcholinesterase inhibition profiles of histamine Schiff bases

In Silico Studies and DNA Cleavage, Antioxidant, Acetylcholinesterase, and Butyrylcholinesterase Activity Evaluation of Bis-Histamine Schiff Bases and Bis-Spinaceamine Substituted Derivatives

Biological Surveying of Diverse Schiff Base Compounds: Antiproliferative, Antiradical and Enzyme Inhibition Activity