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Synthesis and Anti-Mycobacterium Activity of Some New N-Rich Heterocyclic Derivatives and Their Molecular Docking, and DFT Studies

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Abstract

Objective: Synthesis of N-rich heterocyclic derivatives; anti-TB activity, molecular docking, ADME-T, and computational studies. Methods: Synthesis was carried out by conventional method; structures of synthesised was confirmed by different spectroscopic methods; evaluation of anti-TB activity was done by Microplate Alamar Blue assay (MABA); Molecular docking was analyzed by using ChemBioDraw tool (part of the ChemBioOffice Ultra 14.0 suite) and ADME was done by web programme Swiss ADME; DFT studies was carried out by DFT (B3LYP) with the aid of the 6-311++G(d,p) basis set in the Gaussian 09 software. Results: The activity results showed that compounds (IIIc) and (IIIe) demonstrated outstanding activity with MIC values of 1.6 μg/mL, which are closer to the reference standards of rifampicin and streptomycin, while the remaining compounds had reduced efficacy. Discussion: These results show that activity affected by the pyrimidine core and indole moiety of (IIIc) and (IIIe) showed very effective efficacy compared to the reference standards, respectively. Conclusions: Based on the anti-TB activity findings, in-silico molecular docking and ADME profiles, our synthesized drugs followed all five criteria, including high GI absorption, no blood-brain barrier, and minimal skin permeability. Compounds (IIIa) and (IIIb) demonstrated a smaller energy gap in the DFT analysis, indicating that it is chemically more reactive than other compounds. As a result, these compounds demonstrated increased anti-TB activity.

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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ACKNOWLEDGMENTS

The authors would like to thank the Chairman of the Department of Industrial Chemistry at Kuvempu University in Shankaraghatta for providing laboratory facilities, as well as the University of Mysore and Dharwad for providing spectral data.

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This work was supported by regular institutional funding, and no additional grants were obtained.

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Authors and Affiliations

  1. Department of P.G. Studies and Research in Industrial Chemistry, Jnana Sahyadri, Kuvempu University, Shankaraghatta, Shivamogga, 577451, Karnataka, India

    Raghavendra Hegde, Itte Pushpavathi & O. Nagaraja

  2. Department of P.G. Studies and Research in Chemistry, Jnana Sahyadri, Kuvempu University, Shankaraghatta, Shivamogga, 577451, Karnataka, India

    Talavara Venkatesh

  3. Department of P.G. Studies and Research in Biotechnology, Jnana Sahyadri, Kuvempu University Shankaraghatta, Shivamogga, 577451, Karnataka, India

    S. Ravi Kumar

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  1. Raghavendra Hegde
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Methodology, investigation, synthesis, DFT studies, writing-original draft, and supervision by authors RH, IP, TV, and NO.

Molecular docking analysis by author RKS.

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Correspondence to Itte Pushpavathi or Talavara Venkatesh.

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Hegde, R., Pushpavathi, I., Venkatesh, T. et al. Synthesis and Anti-Mycobacterium Activity of Some New N-Rich Heterocyclic Derivatives and Their Molecular Docking, and DFT Studies. Russ J Bioorg Chem 50, 147–161 (2024). https://doi.org/10.1134/S1068162024010199

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