Novel 1,3,4-thiadiazole compounds as potential MAO-A inhibitors - design, synthesis, biological evaluation and molecular modelling


SAĞLIK B. N., KAYA ÇAVUŞOĞLU B., ACAR ÇEVİK U., OSMANİYE D., LEVENT S., ÖZKAY Y., ...More

RSC MEDICINAL CHEMISTRY, vol.11, no.9, pp.1063-1074, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 11 Issue: 9
  • Publication Date: 2020
  • Doi Number: 10.1039/d0md00150c
  • Journal Name: RSC MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1063-1074
  • Anadolu University Affiliated: Yes

Abstract

Monoamine oxidases (MAOs) are important drug targets for the management of neurological disorders. Herein, a series of new 1,3,4-thiadiazole derivatives bearing various alkyl/arylamine moieties as MAO inhibitors were designed and synthesized. All of the compounds were more selective againsthMAO-A thanhMAO-B. The half maximal inhibitory concentration (IC50) values of most of the compounds were lower than that of the common drug moclobemide (IC50= 4.664 mu M) and compound6bwas proven to be the most active compound (IC50= 0.060 mu M). Moreover, it was seen that compound6bshowed a similar inhibition profile to that of clorgyline (IC50= 0.048 mu M). The inhibition profile was found to be reversible and competitive for compound6bwith MAO-A selectivity. Molecular modelling studies aided in the understanding of the interaction modes between compound6band MAO-A. Furthermore, this compound was predicted to have a good pharmacokinetic profile and high BBB penetration. Therefore, such compounds are of interest towards developing new MAO inhibitors.