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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
Zanthoxylum capense constituents with antimycobacterial activity against Mycobacterium tuberculosis in vitro and ex vivo within human macrophages
Journal of Ethnopharmacology, Volume 146, No. 1, Year 2013
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Description
Ethnopharmacological relevance: Zanthoxylum capense Thunb. (Rutaceae) is a medicinal plant traditionally used in Mozambique to treat tuberculosis. Aims of the study: The main aim of the study was to find antimycobacterial lead compounds from Zanthoxylum capense. Another goal was to provide scientific validation for the use of this plant in traditional medicine. Methods and materials: By bioassay-guided fractionation, 16 compounds were isolated and screened for their in vitro antimycobacterial activity against two different strains of Mycobacterium tuberculosis. Their in vitro cytotoxicity to human THP-1 macrophages was also assessed. The compounds with favourable selectivity index values (SI>10) were further investigated for their ability to inhibit the growth of Mycobacterium tuberculosis H37Rv in an intracellular macrophage model of infection. Results: The best results were obtained for a benzophenanthridine alkaloid, decarine (1), and an N-isobutylamide, N-isobutyl-(2E,4E)-2,4-tetradecadienamide (15), which showed high activity against Mycobacterium tuberculosis H37Rv (MIC of 1.6 μg/ml), and a low macrophage cytotoxicity (IC50>60 μg/ml), indicating considerable selective activity. The benzophenanthridine alkaloid 6-acetonyldihydronitidine (6) revealed cytotoxicity (IC50 1.7 μg/ml), despite the determined MIC of 6.2-12.5 μg/ml. In infected macrophages, decarine (1) was able to reduce bacterial survival by almost two log units at a concentration of 6.2 μg/ml 5 days post-drug exposure. Compound 15 exhibited an intermediate activity at drug concentrations ranging from 6.2 to 25 μg/ml. Conclusions: The high antimycobacterial activity of decarine found, both in vitro and ex vivo against mycobacteria, and the low cytotoxicity towards human macrophages indicate that it may be valuable as a lead scaffold for the development of anti-TB drugs. © 2013 Elsevier Ireland Ltd. All rights reserved.
Authors & Co-Authors
Luo, Xuan
Portugal, Lisbon
Faculdade de Farmácia, Universidade de Lisboa
Pires, David
Portugal, Lisbon
Universidade de Lisboa
Aínsa, José Antonio
Spain, Zaragoza
Facultad de Medicina, Universidad de Zaragoza
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias
Gracia, Begoña
Spain, Zaragoza
Facultad de Medicina, Universidad de Zaragoza
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias
Duarte, Noélia Maria
Portugal, Lisbon
Faculdade de Farmácia, Universidade de Lisboa
Mulhovo, Silva
Mozambique
Centro de Estudos Moçambicanos e de Etnociências
Anes, Elsa
Portugal, Lisbon
Universidade de Lisboa
Ferreira, Maria José Umbelino
Portugal, Lisbon
Faculdade de Farmácia, Universidade de Lisboa
Statistics
Citations: 57
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1016/j.jep.2013.01.013
ISSN:
03788741
e-ISSN:
18727573
Research Areas
Health System And Policy
Infectious Diseases
Study Locations
Mozambique