Development of 1-(substituted benzofuran-2-yl)-3-(halogen-substituted phenyl)prop-2-en-1-ones as potent, reversible, and selective MAO-B inhibitors for Parkinson's Disease.
Development of 1-(substituted benzofuran-2-yl)-3-(halogen-substituted phenyl)prop-2-en-1-ones as potent, reversible, and selective MAO-B inhibitors for Parkinson's Disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Kochi, IN · Author affiliation
Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682 041, India.Location evidence
Suncheon, KR · Author affiliation
Department of Pharmacy, College of Pharmacy, SunchonNational University, Suncheon, 57922, Republic of Korea.Location evidence
SA · Author affiliation · country only
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jouf University, Sakaka Al Jouf, 72341, Saudi Arabia.Location evidence
Kirkuk, IQ · Author affiliation
Department of Physiology, Biochemistry, and Pharmacology, College of Veterinary Medicine, University of Kirkuk, Kirkuk, 36001, Iraq.Location evidence
Greater Noida, IN · Author affiliation
School of Pharmacy, Sharda University, Knowledge Park III, Greater Noida, India.Location evidence
Khamis Mushait, SA · Author affiliation
Department of Anesthesia and Operations, College of Applied Medical Sciences, King Khalid University, Khamis Mushait, Kingdom of Saudi Arabia.Location evidence
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Original abstract
Ten halogenated benzofuran derivatives (BF1-BF10) were synthesized and evaluated for their inhibitory activity against monoamine oxidase isoforms. All compounds showed stronger inhibition of MAO-B compared to MAO-A. Among them, BF2 exhibited the most potent MAO-B inhibition (IC₅₀ = 0.082 µM), followed by BF5 (IC₅₀ = 0.095 µM) and BF1 (IC₅₀ = 0.16 µM), with high selectivity indices, particularly BF2 (SI = 1038.05). Kinetic studies revealed that BF2 acts as a competitive inhibitor with a Ki value of 0.083 ± 0.0056 µM. Dialysis experiments confirmed its reversible inhibition profile, comparable to the reference drug Safinamide. Both BF2and BF5 were non-cytotoxic toward L929 cells and demonstrated moderate blood-brain barrier permeability in PAMPA assay. Molecular docking showed stabilization of MAO-B via π-π stacking interactions with Tyr326 and Tyr398, and molecular dynamics simulations further confirmed stable binding of BF2 within the MAO-B active site. Overall, BF2 emerged as a potent, selective, and reversible MAO-B inhibitor, warranting for further investigation.