Antituberculosis agents and an inhibitor of the para-aminobenzoic acid biosynthetic pathway from Hydnocarpus anthelminthica seeds.
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.
Wang
Jun-Feng
JF
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, P. R. China.
Dai
Huan-Qin
HQ
Wei
Yu-Ling
YL
Zhu
Hua-Jie
HJ
Yan
Yong-Ming
YM
Wang
Yue-Hu
YH
Long
Chun-Lin
CL
Zhong
Hui-Min
HM
Zhang
Li-Xin
LX
Cheng
Yong-Xian
YX
D010129:4-Aminobenzoic Acid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D053898:Biosynthetic Pathways / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002478:Cells, Cultured; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D031308:Salicaceae / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry*
D000995:Antitubercular Agents; D010129:4-Aminobenzoic Acid