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

Abstract

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 assayed for antioxidant properties by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical decolarisation assay and metal chelating methods. They were also investigated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase, which are associated with several diseases such as Alzheimer, Parkinson and pigmentation disorders. These benzenesulfonamides showed moderate DPPH radical scavenging and metal chelating activity, and low ABTS cation radical scavenging activity. Compounds 2 b, 3d and 3 h showed inhibitory potency against AChE with % inhibition values of >90. BChE was also effectively inhibited by most of the synthesised compounds with >90% inhibition potency. Tyrosinase was less inhibited by these compounds.

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

“…On the other hand, fluoro substitution on para position (compound 2a ), chloro substitution on meta position (compound 2e ) and 3,4‐dichloro substitution (compound 2f ) (which are an electron withdrawing group) make better AChE and BChE inhibitors as compared to other substitutions that have been studied in the current work. These results against AChE and BChE, exactly compatible with the results of our previous studies [40,41] . Also, the inhibitory effect of all compounds is lower than the positive control TAC.…”

“…The all derivatives (MZ1–MZ11) against enzymes demonstrated efficient inhibition profiles with K I values in the range of 335.76±46.91–771.67±68.78 nM for AChE and 41.74±8.08–102.37±21.26 nM for α‐GLY. In another study of Lolak et al., [40] a series of sulfonamides incorporation 1,3,5‐triazine moieties were shown to have great inhibition potency against BChE with most of the compounds have % inhibition value of >90, which are better than the standard drug galantamine (% inhibition value of 87.86 at 200 μM). Interestingly, 1,3,5‐triazine‐substituted ureido benzenesulfonamides were also shown to have great inhibition potency against BChE and selectivity over AChE enzyme [41] .…”

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

“…[76] Sączewski et al [77] showed the synthesis and anticancer activity of novel alkenyl-1,3,5-triazine derivatives. The most active compounds with 5-nitrofuryl (105) and 5-nitrothienyl group (106) exhibited 50% growth inhibitory activity in low micromolar concentrations against renal cancer A498 cell line and colon cancer cell line COLO 205, respectively. [77] Balaha et al [78] reported two series of tri-amino-substituted 1,3,5-triazine derivatives and evaluated their cytotoxicity against non-small-cell lung cancer.…”

“…The phenyl-substituted compound (5,7-diphenyl-[1,2,4]triazolo [2,3-a] [1,3,5]triazin-5-ylamine, 140) (Figure 15) exhibited the highest antioxidant activity. [105] Lolak et al [106] synthesized a series of 16 novel benzenesulfonamides, incorporating 1,3,5-triazine moieties substituted with aromatic amines, dimethylamine, and morpholine, and evaluated their antioxidant properties. These compounds were assayed for antioxidant properties by using 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay, 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical decolorization assay, and metal chelating methods.…”

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

“…is based on our most recent studies, in which we indicated that novel synthesized 1,3-diaryltriazene-substituted sulphanilamide and metanilamide derivatives have a potent and selective inhibition against one of the most abundant isoform hCA II. [3,25,26] Therefore, in the current work, our aim was to change the sulfonamide group from primary to secondary amine and apply it to hCA I, hCA II, AChE, and α-GLY enzymes, [27][28][29] to see the effect of the binding group against potency and selectivity. We aimed to improve the biological potency of 1,3-dirayltriazene-substituted sulfonamides by changing the amine part from primary to secondary (sulphanilamide to sulfathiazole) and observing the potency of these type of compounds against different metabolic enzymes rather than hCA I and II, such as AChE and α-GLY.…”