Biplab Bhattacharjee1, Jhinuk Chatterjee1, Priya Jacob2, V Krishna Murthy1
1Department of Biotechnology, PES Institute of Technology, Bangalore, India.
2RV College of Engineering, Bangalore, India.
ABSTRACT
NHelicobacter Pylori is a bacterium that causes a chronic low-level inflammation of the stomach lining and is strongly linked to the development of duodenal and gastric ulcers and, stomach cancer. Current treatment is based on multi-drug regimes including acid suppression and antimicrobials. However, rising antimicrobial resistance against many of these drugs increases the desire for new antibiotics. The availability of the complete sequence information of Helicobacter Pylori 26695 proteome (1997) has made it possible to carry out the in silico analysis of its genome for identification of potential drug targets. Past research studies have predicted 8 putative drug targets for Helicobacter pylori. Screening of functional inhibitors against these novel putative drug targets may result in discovery of novel therapeutic compounds that can be effective against the bacteria. The putative drug target structures were not available in PDB. Molecular modeling using Modeller 9v7 was done to generate the modeled structures of these drug targets. Further validation of the structures was done using PROCHECK server & Ramachandran plot showed good percentage of amino acids in the favorable region. About 1200 natural antimicrobials obeying the Lipinski’s rule of 5 were screened against 8 modeled putative drug targets. Ligand-protein interactions were predicted using docking software AutodockVina and Quantum3.3.0. The antimicrobials showing better docking score than the standard antibiotics Amoxicillin & Levofloxacin were further evaluated for hydrogen-bond interactions with the amino acids of the binding pocket of the target protein using Swiss pdb Viewer. IC50 values of the best natural antimicrobials were determined using Quantum 3.3.0. ADME TOX Webbox was used to obtain toxicity, absorption, distribution and metabolism data of these compounds. Five naturally occurring antimicrobial compounds namely humulone, vitexin, capsaicin, colchicine and alpinumisoflavone showed greater binding affinity and better IC50 values for the putative drug targets than the commercial antibiotics. Their high ligand binding affinity to the putative targets introduces the prospect for their use in antimicrobial applications. Vitexin, an apigenin flavone glycoside, found in the passion flower Vitex agnus-castus & Phyllostachys nigra bamboo leaves showed the best docking scores and IC50 values for all the 8 putative drug targets. Further research in vivo and in vitro on the antimicrobial activity of Vitexin has to be performed to concrete the evidence of its therapeutic role against Helicobacter pylori infections. Read more…
