| Abstract
| - A novel series of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)-pyrazole derivatives have beensynthesized and investigated for the ability to inhibit selectively the activity of the A and Bisoforms of monoamine oxidase (MAO). All the synthesized compounds show high activityagainst both the MAO-A and the MAO-B isoforms with Ki values between 27 and 4 nM andbetween 50 and 1.5 nM, respectively, except for a few derivatives whose inhibitory activityagainst MAO-B was in the micromolar range. Knowing that stereochemistry may be animportant modulator of biological activity, we performed the semipreparative chromatographicenantioseparation of the most potent, selective, and chiral compounds. The separatedenantiomers were then submitted to in vitro biological evaluation. The selectivity of the (−)-(S)-1 enantiomer against MAO-B increases twice and a half, while the selectivity of the (−)-(S)-4 enantiomer against MAO-A triples. Both the MAO-A and MAO-B isoforms respectivelyof the 1O5W and 1GOS models deposited in the Protein Data Bank were considered in thecomputational study. The docking study was carried out using several computational approacheswith the aim of proposing possible binding modes of the MAO enantioselective compounds 1and 4.
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