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

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Author(s): Pramod Kumar Sahu, Pranab Kishor Mohapatra, Dhanji P. Rajani, Mukesh Kumar Raval*.

Journal Name: Current Computer-Aided Drug Design

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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 has been 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 isconsideredto be non-toxic with predicted high LD50 value, 12000 mg/kg body weight. The phytochemical is tested for its anti-tubercular activity in vitro. It has MIC9962.5μg/mL against the MtbH37Rv strain.

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

Keywords: Molecular docking, Mycobacterium tuberculosis, Narirutin, Shikimate kinase, Drug-likeness, Toxicity

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(E-pub Ahead of Print)
DOI: 10.2174/1573409915666191025112150
Price: $95

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