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In Silico Pharmacology

, 6:8 | Cite as

Taxifolin as dual inhibitor of Mtb DNA gyrase and isoleucyl-tRNA synthetase: in silico molecular docking, dynamics simulation and in vitro assays

  • Charles Kozhikkadan Davis
  • K. Nasla
  • A. K. Anjana
  • G. K. Rajanikant
Original Research

Abstract

DNA gyrase and aminoacyl-tRNA synthetases are two essential bacterial enzymes involved in DNA replication, transcription and translation. Flavonoids are plant secondary metabolites with variable phenolic structures. In this study, eight flavonoids structurally similar to quercetin were selected and their ADMET properties were evaluated. Molecular docking and free energy calculations were carried out to examine the binding of these flavonoids to the ATP-binding site and editing domain of DNA gyrase and Isoleucyl-tRNA synthetase, respectively. Taxifolin was found out to be the top lead molecule in both the docking studies with a good number of interactions with the active site amino acids. Further, binding of taxifolin to the proteins was extensively studied using 50 ns molecular dynamics simulation. In vitro anti-tuberculosis activity of taxifolin was evaluated and compared with the standard drugs. Minimal inhibition concentration of taxifolin was found to be ≤ 12.5 μg/ml.

Keywords

Tuberculosis DNA gyrase Isoleucyl-tRNA synthetase Flavonoids Taxifolin Dual inhibitor 

Notes

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

Supplementary material

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Supplementary material 1 (JPEG 4133 kb)
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Supplementary material 2 (JPEG 3869 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of BiotechnologyNational Institute of Technology CalicutCalicutIndia
  2. 2.Department of Pharmacognosy and PhytochemistryJamia Salafiya Pharmacy CollegeMalappuramIndia

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