Development of Halogenated-Chalcones Bearing with Dimethoxy Phenyl Head as Monoamine Oxidase-B Inhibitors.
Parkinson’s disease
cytotoxicity
dimethoxy chalcones
molecular docking
monoamine oxidase inhibitor
reversibility
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
16 Sep 2022
16 Sep 2022
Historique:
received:
16
08
2022
revised:
09
09
2022
accepted:
13
09
2022
entrez:
23
9
2022
pubmed:
24
9
2022
medline:
24
9
2022
Statut:
epublish
Résumé
Two series of dimethoxy-halogenated chalcones (DM1−DM20) were synthesized and tested for their ability to inhibit monoamine oxidase (MAOs). Compound DM2 exhibited the most significant inhibition against MAO-B with an IC50 value of 0.067 µM, followed by compound DM18 (IC50 = 0.118 µM), with selectivity index (SI) values of 93.88 and >338.98, respectively. However, none of the substances successfully inhibited MAO-A. The MAO-B inhibitors DM2 and DM18 were competitive and reversible, with Ki values of 0.032 ± 0.004 and 0.045 ± 0.001 µM, respectively. DM2 was non-toxic below 100 µg/mL in the cytotoxic test using the Vero epithelial cell line by the MTT method. According to molecular docking studies, DM2 and DM18 formed very similar conformations within the MAO-B binding pocket, with the ortho-chlorine and ortho-fluorine aromatic rings sandwiched between F168 and Y326. These conformations were predicted to show better interactions with the targeted MAO-B than MAO-A. In particular, the induced-fit docking of the dimethoxy phenyl ring of DM2 facing the hydrophobic pocket made up of FAD, Y398, and Y435 had an impact on F168 in the docking pocket. Taken together, DM2 and DM18 may be suitable candidates for treating neurodegenerative conditions such as Parkinson’s disease.
Identifiants
pubmed: 36145373
pii: ph15091152
doi: 10.3390/ph15091152
pmc: PMC9503132
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Deanship of Scientific Research at Umm Al-Qura University
ID : 22UQU4290565DSR77
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