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J Nat Prod. 2016 Oct 28;79(10):2538-2544. Epub 2016 Oct 18.

Isolation of Acacetin from Calea urticifolia with Inhibitory Properties against Human Monoamine Oxidase-A and -B.

Author information

1
Institute for Computational Molecular Science and Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
2
Department of Pharmaceutical Chemistry, Tanta University , Tanta 31527, Egypt.
3
Laboratorio de Investigación en Productos Naturales, Facultad de Química y Farmacia, University of El Salvador , San Salvador, El Salvador.

Abstract

Calea urticifolia (Asteraceae: Asteroideae) has long been used as a traditional medicine in El Salvador to treat arthritis and fever, among other illnesses. The chloroform extract of the leaves of C. urticifolia showed potent inhibition of recombinant human monoamine oxidases (MAO-A and -B). Further bioassay-guided fractionation led to the isolation of a flavonoid, acacetin, as the most prominent MAO inhibitory constituent, with IC50 values of 121 and 49 nM for MAO-A and -B, respectively. The potency of MAO inhibition by acacetin was >5-fold higher for MAO-A (0.121 μM vs 0.640 μM) and >22-fold higher for MAO-B (0.049 μM vs 1.12 μM) as compared to apigenin, the closest flavone structural analogue. Interaction and binding characteristics of acacetin with MAO-A and -B were determined by enzyme-kinetic assays, enzyme-inhibitor complex binding, equilibrium-dialysis dissociation analyses, and computation analysis. Follow-up studies showed reversible binding of acacetin with human MAO-A and -B, resulting in competitive inhibition. Acacetin showed more preference toward MAO-B than to MAO-A, suggesting its potential for eliciting selective pharmacological effects that might be useful in the treatment of neurological and psychiatric disorders. In addition, the binding modes of acacetin at the enzymatic site of MAO-A and -B were predicted through molecular modeling algorithms, illustrating the high importance of ligand interaction with negative and positive free energy regions of the enzyme active site.

PMID:
27754693
DOI:
10.1021/acs.jnatprod.6b00440
[Indexed for MEDLINE]

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