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

Abstract

In the present 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. K_i values of the compounds towards 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 towards hCA II. K_i values of the Acetazolamide were 282.1±19.7 nM and 103.60±27.6 nM towards both isoenzymes, respectively. The compounds inhibited AChE with K_i 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 the present study might be useful in the design of novel inhibitors against hCA I, hCA II, and AChE.

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4-[5-Aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides TP1-10 were synthesized and biological activities were evaluated on AChE, hCA I and hCA II enzymes. The compounds had demonstrated their inhibitory activities at nanomolar concentrations on AChE, hCA I and hCA II enzymes. The experimrntal and computational findings obtained in the present study might be useful in the design of novel inhibitors against hCA I, hCA II and AChE.

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