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Quantitative Structure–Activity Relationship Model, Molecular Docking Simulation and Computational Design of Some Novel Compounds Against DNA Gyrase Receptor

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Abstract

Time consumed and expenses in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain Mycobacterium tuberculosis (TB). To solve the above problem, Quantitative structure activity relationship (QSAR) is a recent approach developed to discover a novel drug with a better biological against M. Tuberculosis. A validated QSAR model developed in this study to predict the biological activities of some anti-tubercular compounds and to design new hypothetical drugs is influenced with the molecular descriptors; MATS2s, nHBint3, maxtsC, TDB9u, RDF90i and RDF110s. Molecular docking studies was as well carried for all the studied compounds in order to show the interactions and binding modes between the ligand and the receptor (DNA gyrase). The lead compound (compound 41) with higher anti-tubercular activity was observed with prominent binding affinity of − 21.9 kcal/mol compared to the recommended drugs; Isoniazid (− 14.6 kcal/mol). Therefore, compound 41 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 41p was observed with better anti-tubercular activities with more prominent binding affinities of − 24.3 kcal/mol. The findings in the research will be valued to pharmacology, medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in vitro and in vivo test could be carried out to validate the computational results.

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Authors and Affiliations

  1. Chemistry Department, Ahmadu Bello University, Zaria, Nigeria

    Shola Elijah Adeniji, Mustapha Abdullahi & Abdurrashid Haruna

  2. Chemistry Department, Baze University, Abuja, Nigeria

    David Ebuka Arthur

Authors
  1. Shola Elijah Adeniji
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  2. David Ebuka Arthur
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  3. Mustapha Abdullahi
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  4. Abdurrashid Haruna
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Correspondence to Shola Elijah Adeniji.

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Adeniji, S.E., Arthur, D.E., Abdullahi, M. et al. Quantitative Structure–Activity Relationship Model, Molecular Docking Simulation and Computational Design of Some Novel Compounds Against DNA Gyrase Receptor. Chemistry Africa 3, 391–408 (2020). https://doi.org/10.1007/s42250-020-00132-9

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