The synthesis, molecular modelling and investigation of MAO-A/MAO-B selectivity of new hydrazone compounds expected to show impact of monoamine oxidase inhibition

In this study, 16 compounds were synthesized as 2 compounds (Compound 1 and 2) of N'-substitutedbenzylidene-2-(5-chloro-2-benzoxazolinon-3-yl)acetohydrazide, 6 compounds (Compounds 3-8) of 3-(substituted arylmethyleneamino)-1-(2-hydroxy-5-chloro phenyl)imidazolidin-2,4-dione and 8 compounds (Compounds 9-16) of N'-substitutedbenzylidene-3-(5-chloro-2-benzoxazolinon-3-yl)propiohydrazide. Their structures were illuminated with the data from FT-IR, ¹H-NMR and mass spectroscopy and their purity with elemental analysis. The synthesis of the compounds was initiated with 5-chloro-2-benzoxazolinone. Its reaction with ethyl chloroacetate/ethyl 3-bromopropionate in alkaline medium led to an ester derivative which reacted with hydrazine hydrate as 2-(5-chloro-2-benzoxazolinon-3-yl)aceto/propiohydrazide derivatives were obtained. The aimed compounds were obtained through heating of hydrazide derivatives with aromatic aldehydes in acidic medium. The compounds' inhibition effects and selectivities on monoamine oxidase enzyme were determined with in vitro fluorometric method by using human MAO-A and –B isoforms. It was seen that the compounds are more selective against MAO-B enzyme and the derivatives with propiohydrazide chemical structure are more effective. For the more effective compounds 9, 13 and 15, dose study for MAO-B inhibition was performed from 10⁻³ to 10⁻⁹ molar concentration. The binding affinities against MAO-B of all the compounds were examined with the result of molecular docking studies.