Synthesis of chalcone-imide derivatives and investigation of their anticancer and antimicrobial activities, carbonic anhydrase and acetylcholinesterase enzymes inhibition profiles

Abstract

The new 1-(4-(3-(aryl)acryloyl)phenyl)-1H-pyrrole-2,5-diones (5a-g) were prepared from 4'-aminchalcones (3a-g) and screened for biological activities. All compounds (3a-g and 5a-g), except 3d and 3e displayed good cytotoxic activities with IC values in the range of 7.06-67.46 μM. IC value of 5-fluorouracil (5-FU) was 90.36 μM. Moreover, most of compounds 5a-g showed high antibacterial activity with 8-20 mm of inhibition zone (19-25 mm of Sulbactam-Cefoperazone (SCF)). In addition, they showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase I, and II (hCA I and hCA II) isoforms. Also, these compounds demonstrated effective inhibition profiles with Ki values of 426.47-699.58 nM against hCA I, 214.92-532.21 nM against hCA II, and 70.470-229.42 nM against AChE. On the other hand, acetazolamide, clinically used drug, showed a Ki value of 977.77 ± 227.4 nM against CA I, and 904.47 ± 106.3 nM against CA II, respectively. Also, tacrine inhibited AChE showed a Ki value of 446.56 ± 58.33 nM.

Novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes: Synthesis, characterization, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase inhibitory properties

“…Average K i values were calculated from graphs (Table 1). [56] Acetylcholinesterase inhibitors (AChEIs) from natural plant, such as galantamine and TAC, are commonly used in pharmacotherapeutic therapies of alzheimer's disease (AD), whereas no butyrylcholinesterase inhibitors (BChEIs) have been recorded in natural plants. [55] In addition, hCA II is the most TA B L E 1 The enzyme inhibition results of novel amides of 1,1-bis-(carboxymethylthio)-1-arylethanes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) extensively studied and characterized of the hCA isoforms.…”

“…[55] In addition, hCA II is the most TA B L E 1 The enzyme inhibition results of novel amides of 1,1-bis-(carboxymethylthio)-1-arylethanes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) extensively studied and characterized of the hCA isoforms. [58][59][60] [56] Acetylcholinesterase inhibitors (AChEIs) from natural plant, such as galantamine and TAC, are commonly used in pharmacotherapeutic therapies of alzheimer's disease (AD), whereas no butyrylcholinesterase inhibitors (BChEIs) have been recorded in natural plants.…”

Synthesis, characterization, antioxidant, antidiabetic, anticholinergic, and antiepileptic properties of novel N‐substituted tetrahydropyrimidines based on phenylthiourea

“…Three out of the four drugs currently approved for the treatment of AD are based on the inhibition act of acetylcholinesterase (AChE) enzyme. Hence, their efficiency is still limited since the long‐term (for instance, greater than 6 months) efficacy and safety are not entirely clear . Thus, the expansion of effective bioanalytical methods for the analysis of AChE inhibitor compounds in biological samples is significant in determining the pharmacokinetics and bioavailability of these drugs as well as the related compounds, metabolites, and degradation products …”

Inhibitory effects of some drugs on carbonic anhydrase enzyme purified from Kangal Akkaraman sheep in Sivas, Turkey

“…CA inhibitors (CAIs) have been used clinically as antiglaucoma, diuretic, antiobesity drugs, anti‐infective, and anticonvulsant drugs; however, their functions were only recently recorded in the treatment of hypoxic tumor or cancers. CAIs are a class of chemicals or pharmaceuticals that suppress the CA activity …”