Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58) coumarins have been synthesized in high yields (72-99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC 50 values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitro
Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl 3-acyl and 3-carboxyhydrazido coumarin derivatives
Alcaro S;ORTUSO F
2011-01-01
Abstract
Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58) coumarins have been synthesized in high yields (72-99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC 50 values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitroI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
