Benzo[ d ]thiazole-2-carboxamides as new antituberculosis chemotypes inhibiting mycobacterial ATP phosphoribosyl transferase.

Future medicinal chemistry(2022)

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摘要
The screening of antimycobacterial benzo[]thiazole-2-carboxamides against ATP-phosphoribosyl transferase (ATP-PRTase) was conducted. The antitubercular potential of compounds  and against ATP-PRTase was assessed through the determination of half maximal effective concentration (EC) and binding constant (K), as well as competitive inhibitory studies and studies of perturbation of secondary structure, molecular modeling and L-histidine complementation assay.  Compounds and significantly inhibited ATP-PRTase as evidenced by their EC and K values and the perturbation of the secondary structure study. Compound exhibited stronger competitive inhibition toward ATP compared with . The inhibition of the growth of by targeting the L-histidine biosynthesis pathway and molecular modeling studies further supported the inhibition of ATP-PRTase.
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关键词
ATP-PRTase (HisG) inhibition,L-histidine complementation assay,anti-TB drug target,benzo[d]thiazole-2-carboxamides,interaction with secondary structure,molecular docking,molecular dynamics simulation
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