| Abstract: | Isocitrate lyase (ICL) catalyses the first step of the glyoxylate bypass pathway, which reversibly cleaves isocitrate into succinate and glyoxylate. This pathway occurs in a wide range of pathogens and plays a key role in the pathogenesis of Mycobacterium tuberculosis (MTB) suggesting that it may represent a drug target for the treatment of tuberculosis. ICL was cloned, expressed, and purified, and a high‐throughput screen (HTS) developed to screen active extracts derived from traditional Chinese medicines (TCMs) for inhibition of ICL. A colorimetric assay based on the formation of glyoxylate‐phenylhydrazone was used to measure ICL activity. The assay had signal to noise (S/N) of 12.74 and Z′ factor of 0.72, indicating that the assay was suitable for HTS. Screening of a collection of 465 extracts derived from TCMs resulted in the identification of two extracts from Illicium verum Hook.f (Illiciaceae, XHD‐1) and Zingiber officinale Rosc (Zingiberaceae, XHD‐2), which inhibited ICL with IC50 values of 47.7 ± 16.9 and 18.2 ± 0.9 µg/ml, respectively. Drug Dev. Res. 67:818–823, 2006. © 2007 Wiley‐Liss, Inc. |
