Article

Antituberculosis agents and an inhibitor of the para-aminobenzoic acid biosynthetic pathway from Hydnocarpus anthelminthica seeds.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, P. R. China.
Chemistry & Biodiversity (impact factor: 1.8). 08/2010; 7(8):2046-53. DOI:10.1002/cbdv.201000072 pp.2046-53
Source: PubMed

ABSTRACT Investigation on the extracts of Hydnocarpus anthelminthica seeds led to the isolation of three new compounds, anthelminthicins A-C (1-3, resp.), and two known ones, namely chaulmoogric acid (4) and ethyl chaulmoograte (5). Their structures were determined mainly by using spectroscopic techniques. The absolute configuration at the cyclopentenyl moiety of compound 2 was rationalized by quantum calculations. Base hydrolysis, followed by optical-rotation comparison, allowed assignment of the configuration of chaulmoogric-acid moiety of compounds 3 and 5. Biological assays revealed that compounds 1-5 significantly inhibit Mycobacterium tuberculosis (MTB) growth with MIC values of 5.54, 16.70, 4.38, 9.82, and 16.80 microM, respectively. Compound 3 was found to inhibit the pathway between chorismate and para-aminobenzoic acid (pAba) with a MIC value of 11.3 microM, representing a new example of pAba inhibitor isolated from a natural source. All compounds were not toxic to Candida albicans SC5314 at a concentration up to 100 microM.

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    Article: Recent advances in antitubercular natural products.
    Abraham García, Virgilio Bocanegra-García, Jose Prisco Palma-Nicolás, Gildardo Rivera
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    ABSTRACT: Currently, one third of the world's population is infected with Mycobacterium tuberculosis and 8.9-9.9 million new and relapse cases of tuberculosis are reported every year. The emergence of new cases, the increased incidence of multi-drug resistant strains of M. tuberculosis, and the adverse effects of first- and second-line antituberculosis drugs have led to renewed research interest in natural products in the hope of discovering new antitubercular leads. Interestingly, hundreds of natural products, possessing novel, uncommon, and known structural architectures, have been reported to exhibit activity towards non-resistant and multi-drug resistant strains of M. tuberculosis. The present review covers literature published during the last five years about those naturally occurring compounds with reported growth inhibitory activity in vitro towards sensitive and resistant M. tuberculosis strains. Compounds with antitubercular properties at minimal inhibitory concentrations (MICs) of less than 50 μg/mL or 60 μM were selected and grouped according to their source of origin (plants, bacteria, fungi, marine organisms, etc) and chemical type (terpenes, steroids, alkaloids, flavonoids, poliketides, peptides, etc). In some cases, the selection covers those structurally relevant natural products with low bioactivity (MICs of ≤128 μg/mL), and also those semisynthetic derivatives with remarkable antitubercular activity (MICs of ≤10 μg/mL). Additionally, this review includes a special section for those natural products that specifically target genes or enzymes of M. tuberculosis.
    European journal of medicinal chemistry 03/2012; 49:1-23. · 3.27 Impact Factor
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Keywords

Base hydrolysis
 
Biological assays
 
Candida albicans SC5314
 
chaulmoogric acid
 
chaulmoogric-acid moiety
 
compound 2
 
Compound 3
 
compounds
 
compounds 1-5
 
compounds 3
 
ethyl chaulmoograte
 
Hydnocarpus anthelminthica seeds
 
MIC value
 
MIC values
 
natural source
 
new compounds
 
optical-rotation comparison
 
pAba inhibitor
 
para-aminobenzoic acid
 
spectroscopic techniques