Synthesis, molecular modeling, and biological evaluation of 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes

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Abstract

In this study, 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides were synthesized, and inhibition effects on AChE, hCA I, and hCA II were evaluated. Ki values of the compounds toward hCA I were in the range of 24.2 ± 4.6-49.8 ± 12.8 nm, while they were in the range of 37.3 ± 9.0-65.3 ± 16.7 nm toward hCA II. Ki values of the acetazolamide were 282.1 ± 19.7 nm and 103.60 ± 27.6 nm toward both isoenzymes, respectively. The compounds inhibited AChE with Ki in the range of 22.7 ± 10.3-109.1 ± 27.0 nm, whereas the tacrine had Ki value of 66.5 ± 13.8 nm. Electronic structure calculations at M06-L/6-31 + G(d,p)//AM1 level and molecular docking studies were also performed to enlighten inhibition mechanism and to support experimental findings. Results obtained from calculations of molecular properties showed that the compounds obey drug-likeness properties. The experimental and computational findings obtained in this study might be useful in the design of novel inhibitors against hCA I, hCA II, and AChE.

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