Identification of Concomitant Inhibitors against Glutamine Synthetase and Isocitrate Lyase in Mycobacterium tuberculosis from Natural Sources.

Tuberculosis (T.B.) is a disease that occurs due to infection by the bacterium, Mycobacterium tuberculosis (Mtb), which is responsible for millions of deaths every year. Due to the emergence of multidrug and extensive drug-resistant Mtb strains, there is an urgent need to develop more powerful drugs...

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Publicado en:BioMed Research International Vol. 2022; pp. 1 - 15
Autores principales: Chanda, Anesha, Kalita, Sanjib, Mishra, Awdhesh Kumar, Changkakoti, Liza, Sarma, Janayita Biswa, Biswas, Kunal, Kakati, Debashree, Mohanta, Yugal Kishore, Tanti, Bhaben, Mahanta, Saurov, Saravanan, Muthupandian
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 10/3/2022
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 10/3/2022
      vid: 2022
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2022/4661491
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        atl: Identification of Concomitant Inhibitors against Glutamine Synthetase and Isocitrate Lyase in Mycobacterium tuberculosis from Natural Sources.
      aug:
        au:
          Chanda, Anesha
          Kalita, Sanjib
          Mishra, Awdhesh Kumar
          Changkakoti, Liza
          Sarma, Janayita Biswa
          Biswas, Kunal
          Kakati, Debashree
          Mohanta, Yugal Kishore
          Tanti, Bhaben
          Mahanta, Saurov
          Saravanan, Muthupandian
        affil: National Institute of Electronics and Information Technology, Guwahati, 781008 Assam, India
      sug:
        subj:
          Tuberculosis Therapy
          Mycobacterium Tuberculosis
          Plant Extracts Analysis
          Plants, Medicinal Analysis
          Molecular Docking Simulation Methods
          Glutamine Drug Effects
          Tuberculosis, Multidrug-Resistant
          Ligands
          Plant Extracts Pharmacodynamics
          Molecular Structure
      ab: Tuberculosis (T.B.) is a disease that occurs due to infection by the bacterium, Mycobacterium tuberculosis (Mtb), which is responsible for millions of deaths every year. Due to the emergence of multidrug and extensive drug-resistant Mtb strains, there is an urgent need to develop more powerful drugs for inclusion in the current tuberculosis treatment regime. In this study, 1778 molecules from four medicinal plants, Azadirachta indica, Camellia sinensis, Adhatoda vasica, and Ginkgo biloba, were selected and docked against two chosen drug targets, namely, Glutamine Synthetase (G.S.) and Isocitrate Lyase (I.C.L.). Molecular Docking was performed using the Glide module of the Schrӧdinger suite to identify the best-performing ligands; the complexes formed by the best-performing ligands were further investigated for their binding stability via Molecular Dynamics Simulation of 100 ns. The present study suggests that Azadiradione from Azadirachta indica possesses the potential to inhibit Glutamine Synthetase and Isocitrate Lyase of M. tuberculosis concomitantly. The excellent docking score of the ligand and the stability of receptor-ligand complexes, coupled with the complete pharmacokinetic profile of Azadiradione, support the proposal of the small molecule, Azadiradione as a novel antitubercular agent. Further, wet lab analysis of Azadiradione may lead to the possible discovery of a novel antitubercular drug.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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