Publication

Abstract : A series of 13 phenyl substituted thiosemicarbazones () were synthesized and evaluated for their inhibitory potential towards human recombinant monoamine oxidase A and B (MAO-A and MAO-B, respectively) and acetylcholinesterase. The solid state structure of was ascertained by the single X-ray diffraction technique. Compounds and were potent for MAO-A (IC 1.82 ± 0.14) and MAO-B (IC 0.27 ± 0.015 μM), respectively. Furthermore, showed a high selectivity index (SI > 37.0) for MAO-B. The effects of fluorine orientation revealed that (-fluorine) showed 28.2 times higher inhibitory activity than (-fluorine) against MAO-B. Furthermore, inhibitions by and against MAO-A and MAO-B, respectively, were recovered to near reference levels in reversibility experiments. Both and showed competitive inhibition modes, with values of 0.97 ± 0.042 and 0.12 ± 0.006 μM, respectively. These results indicate that and are selective, reversible and competitive inhibitors of MAO-A and MAO-B, respectively. Compounds , and showed moderate inhibition against acetylcholinesterase with IC values of 35.35 ± 0.47, 15.61 ± 0.057 and 26.61 ± 0.338 μM, respectively. Blood-brain barrier (BBB) permeation was studied using the parallel artificial membrane permeation assay (PAMPA) method. Molecular docking studies were carried out using AutoDock 4.2.