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This study reports a rapid and efficient synthesis of four novel aryl Schiff base derivatives. Biological activity and molecular modeling studies were conducted to evaluate the inhibitory effects of these compounds on human carbonic anhydrases (hCA) and cholinesterases. The results indicate that the triazole-ring-containing compounds have strong inhibitory effects on hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) targets. Besides comparing the Schiff bases synthesized in our study to reference molecules, we conducted in silico investigations to examine how these compounds interact with their targets. Our studies revealed that these compounds can occupy binding sites and establish interactions with crucial residues, thus inhibiting the functions of the targets. These findings have significant implications as they can be utilized to develop more potent compounds for treating the diseases that these target proteins play crucial roles in or to obtain drug precursors with enhanced efficacy., (© 2024 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

In this study, a series of novel Schiff base derivatives containing a pyrazolone ring (2a-e) were designed, successfully synthesized for the first time, and characterized by elemental analysis and some spectroscopic methods. These compounds were tested for their inhibitory activities on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and the human carbonic anhydrase isoenzymes I and II (hCA I and II). All synthesized molecules indicated significant inhibition effects with IC 50 values ranging from 14.15 to 107.62 nM against these enzymes. Compound 2d showed the most potent inhibitory activity among the tested molecules toward AChE and BChE (IC 50  = 15.07 and 14.15 nM) compared to the standard drug neostigmine. We determined that the IC 50 values of the tested molecules ranged between 16.86 and 57.96 nM for hCA I and 15.24-46.21 nM for hCA II. As a consequence, we may say that some of the Schiff base derivatives may be used as potential drug candidates in later studies., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

The inhibition of the two human cytosolic carbonic anhydrase (hCA; EC 4.2.1.1) isozymes I and II with some new pyrazoline derivatives was investigated for the first time. The structures of the newly synthesized pyrazoline derivatives were characterized by Fourier transform-infrared spectroscopy, 1 H-/ 13 C-nuclear magnetic resonance, and mass spectrometry, and elemental analysis. Compounds 1-6 showed K i values in the range of 16.4-205.9 nM for hCA I and of 6.08-93.21 nM against hCA II. These hydroxyl and amino group-containing compounds generally were competitive inhibitors. The compounds investigated here showed effective hCA I and II inhibitory effects, in the same range as the clinically used acetazolamide, and might be used as leads for generating enzyme inhibitors, possibly targeting other CA isoforms that have not yet been assayed for their interactions with such agents., (© 2020 Deutsche Pharmazeutische Gesellschaft.)

Glutathione reductase (GR) is responsible for the existence of the reduced glutathione (GSH) molecule, a crucial antioxidant against oxidative stress reagents. The antimalarial activities of some redox active compounds are attributed to their inhibition of antioxidant flavoenzyme GR, and inhibitors are therefore expected to be useful for the treatment of malaria. In this work, a fast and effective synthesis and the GR inhibitory properties of 5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one's aryl Schiff base derivatives are reported. For this aim, the triazol nucleus was obtained, which was substituted with identical groups: ester, hydrazide, and Schiff base system at the N-2 and N-4 nitrogen atoms. The majority of the reactions were carried out by utilizing both microwave and conventional methods in order to compare their yields and reaction times. Beside this, the occuring E/Z geometrical isomers from the CN double bond and the cis/trans amide conformers at the CONH single bond were studied. In the biological activity section of this work, it was found that all synthesized compounds have better inhibitory activity than N,N-bis(2-chloroethyl)-N-nitrosourea against GR; especially, two molecules, 6e and 6f, are the best among them. The evidence indicates that these Schiff base derivatives, with triazole ring, are strong GR inhibitors and novel antimalaria candidates., (© 2018 Deutsche Pharmazeutische Gesellschaft.)

Design and synthesis of a new type of bischalcones as an alternative to natural and synthetic bischalcones are reported for the first time. Key steps involved the solvent-free Claisen-Schmidt condensation of chalcones, and the successful first application of the diazotization-diazocoupling reaction in the synthesis of CNNC-linked bischalcones by simple structural modification of p-aminoacetophenone. The structures of all compounds were confirmed by means of FT-IR, (1) H and (13) C NMR, ESI/MS, and elemental analysis. In addition, the newly synthesized compounds were screened for carbonic anhydrase inhibition activities. Almost all bischalcones exhibited moderate-to-good inhibitory activities., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The antioxidant and radical scavenging activities of the synthesized compounds 3, 5, and 6 were determined by various in vitro assays such as 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid radical (ABTS(·+) ) scavenging, ferric ion (Fe(3+) ) reducing power and ferrous ion (Fe(2+) ) chelating activities. Moreover, these activities were compared to those of standard antioxidants such as butylated hydroxyanisole, butylated hydroxytoluene, and trolox. The results showed that the new compounds (3, 5, and 6) had potential antioxidant activity. Besides, inhibition of the two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II with some nitrobenzene compounds was investigated. Compounds 1-6 showed Ki values in the range of 4.88-193.4 µM and 5.295-54.75 µM for hCA I and hCA II, respectively., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)