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Int J Biol Sci 2011; 7(3):376-382. doi:10.7150/ijbs.7.376

Research Paper

Identification of Mannich Base as a Novel Inhibitor of Mycobacterium Tuberculosis Isocitrate by High-Throughput Screening

Lei Ji1, Quanxin Long1, Dacheng Yang2, Jianping Xie1 ✉

1. Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Enviroment and Bio-Resource of the Three Gorges Area, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China;
2. School of Chemistry and Chemical Engineering, Southwest University, Beibei, Chongqing 400715, China.


Mycobacterium tuberculosis (MTB) remains one of the most significant human pathogens since its discovery in 1882. An estimated 1.5 million people died from tubercle bacillus (TB) in 2006, and globally, there were an estimated 9.27 million incident cases of TB in 2007. Glyoxylate bypass pathway occurs in a wide range of pathogens and plays a key role in the pathogenesis of Mycobacterium tuberculosis. Isocitrate lyase (ICL) can catalyses the first step of this pathway, and reversibly cleaves isocitrate into succinate and glyoxylate. So, ICL may represent a good drug target for the treatment of tuberculosis. ICL was cloned, expressed, and purified, and a high-throughput screen (HTS) developed to screen active molecule from a mannich base compounds library for inhibition of ICL. This assay had signal to noise (S/N) of 650.6990 and Z' factor of 0.8141, indicating that the assay was suitable for HTS. Screening of a collection of 124 mannich base compounds resulted in the identification of one mannich base compound, which has a significant inhibitory activity. So, a new family of compound was first reported to inhibit the activity of Mycobacterium tuberculosis ICL. This family of compound might offer new avenue to explore better anti-tuberculosis and fungi drugs.

Keywords: Isocitrate Lyase, Mycobacterium tuberculosis, Drug Target, High-Throughput Screening, mannich bases.

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How to cite this article:
Ji L, Long Q, Yang D, Xie J. Identification of Mannich Base as a Novel Inhibitor of Mycobacterium Tuberculosis Isocitrate by High-Throughput Screening. Int J Biol Sci 2011; 7(3):376-382. doi:10.7150/ijbs.7.376. Available from