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JAC Advance Access originally published online on January 11, 2007
Journal of Antimicrobial Chemotherapy 2007 59(3):548-552; doi:10.1093/jac/dkl523
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Synergistic antimycobacterial activities of sesquiterpene lactones from Laurus spp.

J. Luna-Herrera1, M. C. Costa2, H. G. González1, A. I. Rodrigues2 and P. C. Castilho3,*

1 Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Prolongacion de Carpio y Plan de Ayala S/N, 11430, México City, Mexico 2 INETI, Instituto Nacional de Engenharia, Tecnologia e Inovação, I.P., Estrada do Paço do Lumiar, 1649-038 Lisboa, Portugal 3 Centro de Química da Madeira, Departamento de Química, Universidade da Madeira, Campus da Penteada, 9000–390, Funchal, Madeira, Portugal

Received 28 August 2006; returned 10 October 2006; revised 26 November 2006; accepted 29 November 2006

* Corresponding author. Tel: +351-291-705149; Fax: +351-291-705102; E-mail: castilho{at}uma.pt

Objectives: The aim of this study was to determine the antimycobacterial potential of laurel oil, its fractions and its two sesquiterpene lactones against several mycobacterial strains and clinical isolates, and to establish the possibility of occurrence of some synergistic effects between those lactones using a modification of the fluorometric Alamar Blue microassay (FMABA).

Methods: The in vitro antimycobacterial activity of whole oil and its fractions and pure active compounds were determined by FMABA. A bioassay-guided fractionation of the traditional preparation of laurel oil from Madeira Islands was performed, yielding pure compounds chemically identified by standard procedures. Synergism of pure compounds was established by X/Y quotient analysis adapted to FMABA.

Results: Sesquiterpene lactones, costunolide and dehydrocostuslactone, were the compounds responsible for the antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MICs of 6.25 and 12.5 mg/L, respectively. Antimycobacterial activity against drug-resistant M. tuberculosis clinical isolates was better for the mixture than for pure compounds.

Conclusions: Both lactones presented synergistic activity, i.e. analysis of relative fluorescence units presented an X/Y value <0.5 at a concentration of 1/8 MIC of each compound in the combination. Establishment of synergism by FMABA represents another application of the microplate Alamar Blue assay.

Keywords: costunolide , dehydrocostuslactone , Alamar Blue , synergism


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