Details

Autor(en) / Beteiligte

• Lan, Jin-Shuai
• Pan, Long-Fei
• Xie, Sai-Sai
• Wang, Xiao-Bing
• Kong, Ling-Yi

Titel

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.