An in silico Approach to Identify Potential NDM-1 Inhibitors to Fight Multidrug Resistant Superbugs

Author(s): Seema Barman, Bonashree Phukan, Partha Sarathi Borah, Minakshi Puzari, Mohan Sharma, Pankaj Chetia*.

Journal Name: Current Drug Therapy

Volume 14 , Issue 1 , 2019

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Graphical 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.

Keywords: Antibiotic resistance, NDM-1, autodock, QSAR, ADMET, ajugasterone-C.

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Article Details

Year: 2019
Page: [79 - 84]
Pages: 6
DOI: 10.2174/1574885513666180514161513
Price: $58

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PDF: 55