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

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.