Novel Mannich bases with strong carbonic anhydrases and acetylcholinesterase inhibition effects: 3-(aminomethyl)-6-{3-[4-(trifluoromethyl)phenyl]acryloyl}-2(3H)- benzoxazolones

Abstract

In this study, a new series of Mannich bases, 3-(aminomethyl)-6-{3-[4-(trifluoromethyl)phenyl]acryloyl}-2( 3H )-benzoxazolones ( 1a–g ), were synthesized by the Mannich reaction. Inhibitory effects of the newly synthesized compounds towards carbonic anhydrases (CAs) and acetylcholinesterase (AChE) enzymes were evaluated to find out new potential drug candidate compounds. According to the inhibitory activity results, K i values of the compounds 1 and 1a–g were in the range of 12.3 ± 1.2 to 154.0 ± 9.3 nM against hCA I, and they were in the range of 8.6 ± 1.9 to 41.0 ± 5.5 nM against hCA II. Ki values of acetazolamide (AZA) that was used as a reference compound were 84.4 ± 8.4 nM towards hCA I and 59.2 ± 4.8 nM towards hCA II. K i values of the compounds 1 and 1a–g were in the range of 35.2 ± 2.0 to 158.9 ± 33.5 nM towards AChE. K i value of Tacrine (TAC), the reference compound, was 68.6 ± 3.8 nM towards AChE. Furthermore, docking studies were done with the most potent compounds 1d , 1g , and 1f (in terms of hCA I, hCA II, and AChE inhibition effects, respectively) to determine the binding profiles of the series with these enzymes. Additionally, the prediction of ADME profiles of the compounds pointed out that the newly synthesized compounds had desirable physicochemical properties as lead compounds for further studies.

The palladium-based complexes bearing 1,3-dibenzylbenzimidazolium with morpholine, triphenylphosphine, and pyridine derivate ligands: synthesis, characterization, structure and enzyme inhibitions

“…To investigate the in vitro inhibition mechanism of the benzimidazolium salt 1 and palladium-based complexes ( 2 – 6 ), kinetic studies were realized with the different concentrations of benzimidazolium salt 1 , palladium-based complexes ( 2 – 6 ), and substrate. IC 50 values and dawning of Lineweaver-Burk curves [ 61 ] were calculated as given previously [ 62 , 63 ]. From the observed data, IC 50 and K i values for benzimidazolium salt 1 and palladium-based complexes ( 2 – 6 ) were computed, and the types of inhibition of both isoenzymes were evaluated as in previous study [ 64 ].…”

Enzyme Inhibition and Antioxidant Activities of Asparagus officinalis L. and Analysis of Its Phytochemical Content by LC/MS/MS

“…However, drugs such as tacrine have ended due to side effects. [19] The study investigated the in vitro effects of extracts on AChE and BChE enzyme activities. According to the results, AE extract had the highest inhibition effect for AChE, while AM extract had the highest inhibition effect for BChE enzyme.…”

“…There are clinical applications of AChE inhibitors in disease suppression. [19] Research has focused on discovering plant-based drugs for treating AD due to their low side effects and antioxidant effects. [20] The carbonic anhydrase enzyme, which has 16 isoenzymes identified in mammals, is a metalloenzyme containing Zn 2 + ion in its structure and catalyzes the reversible conversion of CO 2 to bicarbonate and proton.…”

Benzimidazolium Salts Containing Trifluoromethoxybenzyl: Synthesis, Characterization, Crystal Structure, Molecular Docking Studies and Enzymes Inhibitory Properties

“…High or low levels of CAs are frequently linked to different disorders [33,34] . Recently, CAs have been recognized as pharmacological targets, and numerous CA inhibitors (CAIs), the majority of which are sulfonamides, have been used clinically to treat a variety of disorders, including anti‐obesity, anticonvulsant, edema and glaucoma, and as anticancer medications [35–37] . Commercially utilized CAIs typically do not have a high level of selectivity for a single isoenzyme, researchers are constantly looking for new molecules to create isoenzyme‐specific drugs that do not have unwanted side effects [38,39] …”