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Design and in vitro evaluation of possible MAOB activity of 1,3,4-oxadiazole derivatives and melatonin analogues

Valentin R. Karabelyov

  Based on our previous investigation, two different classes of compounds - 1,3,4-oxadiazole derivatives (3a-3e) and melatonin analogues (5a-5e) were synthesized and evaluated for their neuroprotective effect. The aim of our study was to investigate activity in vitro of novel compounds on hMAOB enzyme. Monoaminoxidase activity assay of recombinant human MAOB was performed using a fluorometric method by Amplex UltraRed reagent [1] with small modifications, where Tyramine hydrochloride was used as a substrate. Of the substances tested, 3a and 3d exhibit a statistically significant inhibitory effect on MAOB, commensurate with that of selegiline. The results suggest that some of the oxadiazoles may show promising results in other in vitro models resembling Parkinson's disease.

References: [1]. Bautista-Aguilera, et al., (2014). Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil–indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease. European journal of medicinal chemistry, 75, 82-95.