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Synthesis and evaluation of 6-methylcoumarin derivatives as potent and selective monoamine oxidase B inhibitors
Ist Teil von
MedChemComm, 2015-04, Vol.6 (4), p.592-600
Erscheinungsjahr
2015
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
A new series of 6-methyl-3-phenylcoumarins ( 3a–c and 5a–o ) and 6-methyl-3-heteroarylcoumarins ( 5p–s ) have been designed, synthesized and evaluated as monoamine oxidase inhibitors. The results demonstrated that a large proportion of the synthesized compounds selectively inhibited monoamine oxidase B with IC 50 values in the sub-micromolar range. Among them, compound 5n (IC 50 = 0.0601 μM) exhibited the most potent inhibitory activity and the highest selectivity for monoamine oxidase B (SI > 1664-fold). In addition, the possible binding model of the active compound 5n was measured by docking it into the active site of the hMAO-B complex structure. The results showed that compound 5n interacted with the well-known binding pocket of MAO-B, and a π–π interaction was found between the phenyl ring at position 3 of the coumarin and the phenyl ring of Tyr 326. Consequently, we supplied useful information about the interaction between the enzyme and inhibitor, and developed the 6-methyl-3-phenylcoumarin scaffold as an agent for multifaceted brain disorders.
Sprache
Englisch
Identifikatoren
ISSN: 2040-2503
eISSN: 2040-2511
DOI: 10.1039/C4MD00437J
Titel-ID: cdi_crossref_primary_10_1039_C4MD00437J
Format
–
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