Naphthoquinones isolated from Diospyros anisandra exhibit potent activity against pan-resistant first-line drugs Mycobacterium tuberculosis strains
Autor: | Francisco González-Salazar, Rocío Borges-Argáez, Javier Vargas-Villarreal, M. Méndez-González, Andrés Humberto Uc-Cachón, Salvador Said-Fernández, Mirbella Cáceres-Farfán, Gloria María Molina-Salinas |
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Rok vydání: | 2014 |
Předmět: |
Male
Pulmonary and Respiratory Medicine Antitubercular Agents Microbial Sensitivity Tests Pharmacology Gas Chromatography-Mass Spectrometry Microbiology Mycobacterium tuberculosis Minimum inhibitory concentration chemistry.chemical_compound Chlorocebus aethiops Tuberculosis Multidrug-Resistant medicine Animals Humans Pharmacology (medical) Cytotoxicity Medicinal plants Vero Cells Cells Cultured Plant Stems biology Plant Extracts Biochemistry (medical) Plumbagin Diospyros Middle Aged biology.organism_classification Multiple drug resistance chemistry Leukocytes Mononuclear Plant Bark Vero cell Rifampin Rifampicin Naphthoquinones medicine.drug |
Zdroj: | Pulmonary Pharmacology & Therapeutics. 27:114-120 |
ISSN: | 1094-5539 |
Popis: | Background and objectives The recent emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) Mycobacterium tuberculosis (MTB) strains have further complicated the control of tuberculosis (TB). There is an urgent need of new molecules candidates to be developed as novel, active, and less toxic anti-tuberculosis (anti-TB) drugs. Medicinal plants have been an excellent source of leads for the development of drugs, particularly as anti-infective agents. In previous studies, the non-polar extract of Diospyros anisandra showed potent anti-TB activity, and three monomeric and five dimeric naphthoquinones have been obtained. In this study, we performed bioguided chemical fractionation and the isolation of eight naphthoquinones from D. anisandra and their evaluation of anti-TB and cytotoxic activities against mammalian cells. Methods The n-hexane crude extract from the stem bark of the plant was obtained by maceration and liquid–liquid fractionation. The isolation of naphthoquinones was carried out by chromatographic methods and identified by gas chromatography and mass spectroscopy data analysis. Anti-TB activity was evaluated against two strains of MTB (H37Rv) susceptible to all five first-line anti-TB drugs and a clinical isolate that is resistant to these medications (pan-resistant, CIBIN 99) by measuring the minimal inhibitory concentration (MIC). Cytotoxicity of naphthoquinones was estimated against two mammalian cells, Vero line and primary cultures of human peripheral blood mononuclear (PBMC) cells, and their selectivity index (SI) was determined. Results Plumbagin and its dimers maritinone and 3,3′-biplumbagin showed the strongest activity against both MTB strains (MIC = 1.56–3.33 μg/mL). The bioactivity of maritinone and 3,3′-biplumbagin were 32 times more potent than rifampicin against the pan-resistant strain, and both dimers showed to be non-toxic against PBMC and Vero cells. The SI of maritinone and 3,3′-biplumbagin on Vero cells was 74.34 and 194.11 against sensitive and pan-resistant MTB strains, respectively. Conclusion Maritinone and 3,3′-biplumbagin possess a very interesting potential for development as new drugs against M. tuberculosis, mainly resistant profile strains. |
Databáze: | OpenAIRE |
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