Investigation of the anti-TB potential of selected propolis constituents using a molecular docking approach

Mohammad Tuhin Ali,Jamil A Shilpi,Natalia Blicharska,Veronique Seidel

doi:10.1038/s41598-018-30209-y

Abstract

Human tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading bacterial killer disease worldwide and new anti-TB drugs are urgently needed. Natural remedies have long played an important role in medicine and continue to provide some inspiring templates for drug design. Propolis, a substance naturally-produced by bees upon collection of plant resins, is used in folk medicine for its beneficial anti-TB activity. In this study, we used a molecular docking approach to investigate the interactions between selected propolis constituents and four ‘druggable’ proteins involved in vital physiological functions in M. tuberculosis, namely MtPanK, MtDprE1, MtPknB and MtKasA. The docking score for ligands towards each protein was calculated to estimate the binding free energy, with the best docking score (lowest energy value) indicating the highest predicted ligand/protein affinity. Specific interactions were also explored to understand the nature of intermolecular bonds between the most active ligands and the protein binding site residues. The lignan (+)-sesamin displayed the best docking score towards MtDprE1 (−10.7 kcal/mol) while the prenylated flavonoid isonymphaeol D docked strongly with MtKasA (−9.7 kcal/mol). Both compounds showed docking scores superior to the control inhibitors and represent potentially interesting scaffolds for further in vitro biological evaluation and anti-TB drug design.

Highlights

Human tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading cause of deaths worldwide from a single infectious agent
The propolis constituents investigated in this study represent some structurally diverse compounds that we grouped into four main categories, namely flavonoids, terpenoids, simple phenolics and miscellaneous substances including a pterocarpan, a phenylethanoid derivative, five stilbenes and four lignans
In order to validate the docking conditions prior to virtually screening the propolis constituents, each control inhibitor was retrieved from its co-crystallised complex and re-docked using the AutoDock Vina software against the relevant target

Summary

Introduction

Human tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading cause of deaths worldwide from a single infectious agent. Treating TB is a long process that involves complex drug regimens, with adverse effects and interactions, and is associated with poor patient compliance. There remains an urgent need to discover and develop new anti-TB drugs, to target drug-resistant and dormant strains of M. tuberculosis as well as providing a more effective and shorter duration of treatment[2]. Natural remedies, sourced from plants, microbes and animal products, have for centuries played an important role in medicine. They represent a unique pool of highly-diverse chemicals that have evolved to interact with biological targets and that continue to provide some new and inspiring templates for pharmaceutical drug design[3]. The docking of propolis constituents towards MtPanK, MtDprE1, MtPknB and MtKasA, has never been reported

Methods

Results

Conclusion