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

Chem Biodivers. 2010 Aug;7(8):2046-53. doi: 10.1002/cbdv.201000072.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminobenzoic Acid / antagonists & inhibitors*
  • 4-Aminobenzoic Acid / chemistry
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Biosynthetic Pathways / drug effects
  • Candida albicans / drug effects
  • Cells, Cultured
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Salicaceae / chemistry*
  • Seeds / chemistry*

Substances

  • Antitubercular Agents
  • 4-Aminobenzoic Acid