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Monoamine oxidase inhibition by thiazole derivatives substituted with the benzenesulfonamide moiety

  • Anton Shetnev,
  • Julia Efimova,
  • Olga Gasilina,
  • Eugenia Shabalina,
  • Sergey Baykov,
  • Dmitry Lifanov,
  • Elena Petersen,
  • Mikhail Korsakov,
  • Anél Petzer,
  • Jacobus P. Petzer

摘要

Based on a report that 1,3,4-oxadiazol-2-ylbenzenesulfonamides act as inhibitors of monoamine oxidase B (MAO-B), the present study explored the effect of replacing the 1,3,4-oxadiazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized and evaluated as in vitro inhibitors of the human MAOs. The results showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of MAO-B with the most potent MAO-B inhibitor presenting with an IC50 value of 0.103 µM (3j). Potent MAO-B inhibition was obtained with the substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concluded that 1,3-thiazolylbenzenesulfonamides may serve as lead MAO inhibitors for the development of new treatments for disease states such as Parkinson’s disease.