Abstract
The emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis is the main reason why tuberculosis (TB) continues to be a major health problem worldwide. It is urgent to discover novel anti-mycobacterial agents based on new drug targets for the treatment of TB, especially MDR-TB. Tryptophan biosynthetic pathway, which is essential for the survival of M. tuberculosis and meanwhile absent in mammals, provides potential anti-TB drug targets. One of the promising drug targets in this pathway is anthranilate synthase component I (TrpE), whose role is to catalyze the conversion of chorismate to anthranilate using ammonia as amino source. Anthranilate synthase is an interesting target enzyme for antimicrobial activity due to its presence in microorganisms for the synthesis of the essential amino acid tryptophan. In the present study three compounds Cannabigerolic acid, cannabinolic acid and adhumulone from Cannabis sativa have been used for insilio docking studies. Inhibitory studies (invitro) of these compounds against Microorganism have reported earlier. Our approach is to find out the compounds inhibiting the AS1 of MTB by insilico docking and also find out compounds having similar pharmacophore characters from ZINC database so that those compounds can be procured of synthesized in laboratory and used for AS1 inhibitor studies. This study shows that AS can be used as a target enzyme to investigate the mode of action of our compounds in MTB.
Highlights
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), remains one of the most devastating global diseases
About one-third of the world population is infected with M. tuberculosis and almost 5000 people die from TB everyday (Corbett et al, 2003)
Long-term antibiotic therapy has led to the emergence and wide spread of multi-drug resistant (MDR) M. tuberculosis strains
Summary
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), remains one of the most devastating global diseases. Long-term antibiotic therapy has led to the emergence and wide spread of multi-drug resistant (MDR) M. tuberculosis strains. Discovery of novel anti-mycobacterial agents based on new drug targets is an urgent task to combat TB, especially MDR-TB. Anthranilate synthase (AS 1, EC 4.1.3.27), a member of tryptophan biosynthetic pathway, catalyzes the formation of anthranilate from chorismate and ammonia (or glutamine), which is the first committed step branching from the common aromatic amino acid (shikimate) pathway toward the biosynthesis of l-tryptophan. AS from microorganisms are made up of synthase component (TrpE) and glutamine amidotransferase component (TrpG), namely component I and component II, respectively (Morollo and Eck 2001; Spraggon et al, 2001; Knochel et al, 1999). TrpE is able to catalyze the synthesis of anthranilate with ammonia as the source of nitrogen atom independently (Knochel et al, 1999; Ito et al, 1969; Hankins and Mills 1976)
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