2. Academic Validation
  3. Structure-based Discovery of Narirutin as a Shikimate kinase Inhibitor with Anti-tubercular Potency

Structure-based Discovery of Narirutin as a Shikimate kinase Inhibitor with Anti-tubercular Potency

  • Curr Comput Aided Drug Des. 2020;16(5):523-529. doi: 10.2174/1573409915666191025112150.
Pramod Kumar Sahu 1,  Pranab Kishor Mohapatra 2,  Dhanji Popatbhai Rajani 3,  Mukesh Kumar Raval 1
Affiliations

Affiliations

  • 1 Department of Chemistry, Gangadhar Meher University, Sambalpur, 768004, Odisha, India
  • 2 Department of Chemistry, CV Raman College of Engineering, Bidyanagar, Mahura, Janla, Bhubaneswar 752054, Odisha, India
  • 3 Microcare Laboratory and Tuberculosis Research Center, 105, Manthan Point, Unapani Road, Lal Darwaja, Surat - 395003, Gujarat, India
PMID: 31654517 DOI: 10.2174/1573409915666191025112150
Abstract

Background: Shikimate pathway is essential for tubercular bacillus but it is absent in mammals. Therefore, Shikimate kinase and other enzymes in the pathway are potential targets for the development of novel anti-tuberculosis drugs.

Objective: In the present study, Shikimate kinase is selected as the target for in silico screening of phytochemicals with an aim to discover a novel herbal drug against Mycobacterium tuberculosis (Mtb).

Methods: A structure-based drug discovery approach is undertaken for the execution of the objective. Virtual screening of phytochemical database NPACT against the target, Shikimate kinase (PDB ID 3BAF), is carried out followed by toxicity and drug-likeness filtration. Finally, a lead, narirutin was selected for in vitro anti-tubercular study.

Results: Narirutin, present in citrus fruits, emerges as the lead. It is considered to be non-toxic with predicted high LD50 value, 12000 mg/kg body weight. The phytochemical is tested for its antitubercular activity in vitro. It has MIC99 62.5 μg/mL against the MtbH37Rv strain.

Conclusion: This is the first-ever report to show anti-tuberculosis potency of narirutin.

Keywords

Molecular docking; Mycobacterium tuberculosis; drug-likeness; narirutin; shikimate kinase; toxicity.

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