Mycobacterium tuberculosis isocitrate lyase lead inhibitor

Abstract

The invention discloses a mycobacterium tuberculosis isocitrate lyase lead inhibitor, the chemical name of which is 7, 8-dihydroxy coumarin, and the chemical name of which is daphnetin and daphne giraldii nitsche A. The invention also discloses a preparation method of the mycobacterium tuberculosis isocitrate lyase lead inhibitor. The half inhibition concentration of the 7, 8-dihydroxy coumarin to mycobacterium tuberculosis isocitrate lyase is 3.34 +/-1.46 mu g/mL, and the activity of the 7, 8-dihydroxy coumarin is 2 times that of itaconic acid and 3.3 times that of 3-bromopyruvic acid; the MIC (minimal inhibitory concentration) value of the mycobacterium smegmatis resistance is 128 mu g/mL; molecular docking results show that the 7, 8-dihydroxy coumarin has strong interaction with key amino acid residues of active sites of the mycobacterium tuberculosis isocitrate lyase; research results show that the 7, 8-dihydroxy coumarin is expected to be developed into the latent mycobacterium tuberculosis resisting medicine after being further modified.

Description

technical field [0001] The invention relates to the technical field of medicine, and mainly describes a leading compound of the natural product of Mycobacterium tuberculosis isocitrate lyase, 7,8-dihydroxycoumarin, which has strong Mycobacterium tuberculosis isocitrate lyase Enzyme inhibitory activity and moderate antibacterial activity. Background technique [0002] Tuberculosis is caused by the deadly Mycobacterium tuberculosis (Mtb) pathogen and remains one of the world's deadliest infectious diseases. Currently, although the incidence of tuberculosis has declined, the increasing number of drug-resistant strains, especially multidrug-resistant (MDR) and super-drug-resistant (XDR) strains, has brought great challenges to the treatment of tuberculosis. The current standard treatment for drug-susceptible TB lasts for 6 months, including 2 months of rifampicin, isoniazid, ethambutol, pyrazinamide, followed by rifampicin and isoniazid for at least 4 months before complete Er...

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Problems solved by technology

However, these inhibitors have weak inhibitory ability and strong bio

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