Title:An in silico Approach to Identify Potential NDM-1 Inhibitors to Fight Multidrug Resistant Superbugs
VOLUME: 14 ISSUE: 1
Author(s):Seema Barman, Bonashree Phukan, Partha Sarathi Borah, Minakshi Puzari, Mohan Sharma and Pankaj Chetia*
Affiliation:Centre for Biotechnology and Bioinformatics, Dibrugarh University, Dibrugarh, 786004, Assam, Centre for Biotechnology and Bioinformatics, Dibrugarh University, Dibrugarh, 786004, Assam, Centre for Biotechnology and Bioinformatics, Dibrugarh University, Dibrugarh, 786004, Assam, Department of Life Sciences, Dibrugarh University, Dibrugarh, 786004, Assam, Department of Life Sciences, Dibrugarh University, Dibrugarh, 786004, Assam, Department of Life Sciences, Dibrugarh University, Dibrugarh, 786004, Assam
Keywords:Antibiotic resistance, NDM-1, autodock, QSAR, ADMET, ajugasterone-C.
Abstract:Background: Antibiotic resistance is a global threat and the emergence of
Multi-Drug Resistant (MDR) bacteria compromises the treatment options, limiting the
number of available drugs. New Delhi Metallo-beta-lactamase-1 (NDM-1) mediated drug
resistance is one of the mechanisms associated with multidrug resistance.
Objective: In our study, reverse chemogenomics technique was applied for identification
of potential NDM-1 inhibitors from plant sources to combat the issue of drug resistance in
Gram-negative bacteria.
Method: Computational methodologies were employed to understand and validate the
molecular interaction between the target protein and the ligands. A total of 22 plant-based
compounds were screened for inhibitory activity against NDM-1 through subsequent
comparative molecular docking. The compounds were passed through Lipinski filter and
ADME-Tox filter, which represent an important part of drug discovery.
Result: On the basis of optimum molecular docking values, Garcinol was recognized as
the most potential NDM-1 inhibitor. However, in Quantitative-Structure Activity Relationship
assessment, Ajugasterone-C showed the least value of minimum inhibitory concentration.
Most of the compounds were found to comply with Lipinski rule of 5 and
showed good results in ADME-Tox filtration.
Conclusion: Garcinol and Ajugasterone-C were found to possess drug like characteristics
and can act as potential NDM-1 inhibitors.
