Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives

  • Eur J Med Chem. 2011 Oct;46(10):4846-52. doi: 10.1016/j.ejmech.2011.07.017.
Daniela Secci  1 ,  Simone Carradori ,  Adriana Bolasco ,  Paola Chimenti ,  Matilde Yáñez ,  Francesco Ortuso ,  Stefano Alcaro
Affiliations
  • 1. Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma Sapienza, P.le A. Moro 5, 00185 Rome, Italy. [email protected]
PMID: 21872365 DOI: 10.1016/j.ejmech.2011.07.017
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 vitro.

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