In:
Chemical Biology & Drug Design, Wiley, Vol. 102, No. 2 ( 2023-08), p. 271-284
Kurzfassung:
Eight derivatives of benzyloxy‐derived halogenated chalcones ( BB1‐BB8 ) were synthesized and tested for their ability to inhibit monoamine oxidases (MAOs). MAO‐A was less efficiently inhibited by all compounds than MAO‐B. Additionally, the majority of the compounds displayed significant MAO‐B inhibitory activities at 1 μM with residual activities of less than 50%. With an IC 50 value of 0.062 μM, compound BB4 was the most effective in inhibiting MAO‐B, followed by compound BB2 (IC 50 = 0.093 μM). The lead molecules showed good activity than the reference MAO‐B inhibitors (Lazabemide IC 50 = 0.11 μM and Pargyline Pargyline IC 50 = 0.14). The high selectivity index (SI) values for MAO‐B were observed in compounds BB2 and BB4 (430.108 and 645.161, respectively). Kinetics and reversibility experiments revealed that BB2 and BB4 were reversible competitive MAO‐B inhibitors with K i values of 0.030 ± 0.014 and 0.011 ± 0.005 μM, respectively. Swiss target prediction confirmed the high probability in the targets of MAO‐B for both compounds. Hypothetical binding mode revealed that the BB2 or BB4 is similarly oriented to the binding cavity of MAO‐B. Based on the modelling results, BB4 showed a stable confirmation during the dynamic simulation. From these results, it was concluded that BB2 and BB4 were potent selective reversible MAO‐B inhibitors and they can be considered drug candidates for treating related neurodegenerative diseases such as Parkinson's disease.
Materialart:
Online-Ressource
ISSN:
1747-0277
,
1747-0285
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2023
ZDB Id:
2216600-2
SSG:
12
