Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents

Noorullah Baig; Rajnish Prakash Singh; Subhash Chander; Prabhat Nath Jha; Sankaranarayanan Murugesan; Ajay K Sah

doi:10.1016/j.bioorg.2015.10.002

Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents

Bioorg Chem. 2015 Dec:63:110-5. doi: 10.1016/j.bioorg.2015.10.002. Epub 2015 Oct 9.

Authors

Noorullah Baig¹, Rajnish Prakash Singh², Subhash Chander³, Prabhat Nath Jha², Sankaranarayanan Murugesan³, Ajay K Sah⁴

Affiliations

¹ Department of Chemistry, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan 333031, India.
² Department of Biological Science, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan 333031, India.
³ Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan 333031, India.
⁴ Department of Chemistry, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan 333031, India. Electronic address: asah@pilani.bits-pilani.ac.in.

PMID: 26476390
DOI: 10.1016/j.bioorg.2015.10.002

Abstract

Six amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(-)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity.

Keywords: Amino acids; Antibacterial; Glucopyranosylamine; Kinetics; Molecular docking; N-glycoconjugates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / chemistry*
Amino Acids / pharmacology
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Dose-Response Relationship, Drug
Escherichia coli / drug effects
Glucose / chemistry*
Glucose / pharmacology
Glycoconjugates / chemical synthesis
Glycoconjugates / chemistry*
Glycoconjugates / pharmacology*
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Klebsiella pneumoniae / drug effects
Microbial Sensitivity Tests
Molecular Docking Simulation*
Molecular Structure
Structure-Activity Relationship

Substances

Amino Acids
Anti-Bacterial Agents
Glycoconjugates
Glucose