A novel series of sulfonamides, 4‐(3‐phenyltriaz‐1‐en‐1‐yl)‐N‐(4‐methyl‐2‐pyrimidinyl)benzenesulfonamides (1–9), was designed and synthesized by the diazo reaction between sulfamerazine and substituted aromatic amines for the first time. Their chemical structures were characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, and high‐resolution mass spectra. The newly synthesized compounds were evaluated in terms of acetylcholineasterase (AChE) and human carbonic anhydrases (hCA) I and II isoenzymes inhibitory activities. According to the AChE inhibition results, the Ki values of the compounds 1–9 were in the range of 19.9 ± 1.5 to 96.5 ± 20.7 nM against AChE. Tacrine was used as the reference drug and its Ki value was 49.2 ± 2.7 nM against AChE. The Ki values of the compounds 1–9 were in the range of 10.2 ± 2.6 to 101.4 ± 27.8 nM against hCA I, whereas they were 18.3 ± 4.4 to 48.1 ± 4.5 nM against hCA II. Acetazolamide was used as a reference drug and its Ki values were 72.2 ± 5.4 and 52.2 ± 5.7 nM against hCA I and hCA II, respectively. The most active compounds, 1 (nonsubstituted) against AChE, 5 (4‐ethoxy‐substituted) against hCA I, and 8 (4‐bromo‐substituted) against hCA II, were chosen and docked at the binding sites of these enzymes to explain the inhibitory activities of the series. The newly synthesized compounds presented satisfactory pharmacokinetic properties via the estimation of ADME properties.

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Aims Flavonoids and related compounds, such as quercetin‐based antiviral drug Gene‐Eden‐VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS‐CoV proteases. In this study, we aimed to compare the anti‐SARS CoV‐2 activities of both newly synthesized chalcone derivatives and these two drugs. Methods Determination of the potent antiviral activity of newly synthesized chalcone derivatives against SARS‐CoV‐2 by calculating the RT‐PCR cycling threshold ( C t ) values. Results Antiviral activities of the compounds varied because of being dose dependent. Compound 6 , 7 , 9 , and 16 were highly effective against SARS‐CoV‐2 at the concentration of 1.60 µg/mL. Structure‐based virtual screening was carried out against the most important druggable SARS‐CoV‐2 targets, viral RNA‐dependent RNA polymerase, to identify putative inhibitors that could facilitate the development of potential anti‐coronavirus disease‐2019 drug candidates. Conclusions Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from −4.370 to −2.748 kcal/mol along with their toxicological, ADME, and drug‐like properties.

A series of compounds incorporating 3-(3-(2/3/4-substituted phenyl)triaz-1-en-1-yl) benzenesulfonamide moieties were synthesised and their chemical structure was confirmed by physico-chemical methods. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were evaluated against human isoforms hCA I and II. K I values of these sulphonamides were in the range of 21 ± 4-72 ± 2 nM towards hCA I and in the range of 16 ± 6-40 ± 2 nM against hCA II. The 4-fluoro substituted derivative might be considered as an interesting lead due to its effective inhibitory action against both hCA I and hCA II (K I s of 21 nM), a profile rarely seen among other sulphonamide CA inhibitors, making it of interest in systems where the activity of the two cytosolic isoforms is dysregulated.

The aim of this study was to design new molecules and evaluate their anticholinesterase and amyloid beta (Aβ) inhibition activities as multifunctional drug candidates for the treatment of Alzheimer's disease (AD). A series of 5,6-dimethoxy-1H-indene-2-carboxamides (1-22) was synthesized; cholinesterase inhibitory activities of the compounds were measured according to Ellman's colorimetric assay, while the thioflavin T assay was used for measuring the inhibition of Aβ aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds 20 and 21 were found to be the most potent BuChE inhibitors with respective IC values of 1.08 and 1.09 μM. Compounds 16, 20, 21 and 22 exhibited remarkable inhibition of Aβ aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor 20 displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound 20 may be an especially promising multifunctional drug for the prevention and treatment of AD.