In Silico Screening of New Delhi metallo- β – lactamase-1(NDM-1) Inhibitors with Drug Reporposing Strategy
Özet
Background/Aim: Excessive and improper use of antibiotics in both agricultural and clinical areas
has resulted in a rise in bacterial strains that are resistant to several drugs. Among these strains,
gram-negative bacteria that produce β-lactamase have become the most common. Given the signifi-
cant role of metallo-β-lactamases in biomedicine, it has become imperative to identify inhibitors for
these enzymes. NDM1 has exhibited the most rapid and extensive global dissemination among all
metallo-β-lactamases, leading to the rapid emergence of bacterial infections containing plasmid-en-
coded NDM1 worldwide. Therefore, the goal of this study is to
discover novel and potent inhibitors of NDM1 by employing virtual screening techniques on existing
drugs.
Materials and Method: For screening, the 4EXS crystal structure was selected based on information
from the literature. All compounds (10767) in the Drugbank database were downloaded and prepared
using the LigPrep module. The docking analyses were conducted with Glide’s HTVS/SP/XP docking
modules to identify compounds with the highest protein binding, and their effects on the E. coli strain
containing the NDM-1 plasmid were assessed and the minimum inhibitory concentrations (MIC’s)
determined. Also, the synergistic effects of the drugs were examined with the checkerboard method.
Results: In the virtual screening, it was determined that NADH, Pemetrexed, and Zoledronic acid
were hit drugs. The effects of the drugs were examined on the resistant E.coli
strain, and Zoledronic acid was found to be the most effective. MIC values were determined as
Ampicillin512, Meropenem16, Imipenem256, Cefotaxime64, NADH>1024, Zoledronic Acid128, and
Pemetrexed>1024. Zoledronic acid was found to have additive effects with Ampicillin, synergistic
effects with Meropenem, indifference effects with Imipenem, and additive effects with Cefotaxime
with the checkerboard method.
Conclusion: This study has shown that Zoledronic acid and Meropenem can be used in combination
against
E.coli strains containing NDM-1 plasmid and that they may be potential therapeutic agents.
Atatürk University BAP unit (ProjectID:FBA-2020-8419) financed this research.
Keywords: NDM-1, Virtual Screening, Drug Reporposing, Ecoli, In Vitro
Atıf için künye
Babaoğlu, Z. Y., Özpolat, Ö. F., Demirelli, Ş., Taş Özdemir, T., Uslu, H., & Kılıç, D. (2024). In Silico Screening of New Delhi metallo- β – lactamase-1(NDM-1) Inhibitors with Drug Reporposing Strategy. 9th International Congress of the Molecular Biology Association of Turkey, İzmir (ss. 127).
BibTeX
@inproceedings{babaoglu2024-236132,
author = {Babaoğlu, Zeynep Yağmur and Özpolat, Özgür Fırat and Demirelli, Şeyma and Taş Özdemir, Tuğba and Uslu, Hakan and Kılıç, Deryanur},
title = {In Silico Screening of New Delhi metallo- β – lactamase-1(NDM-1) Inhibitors with Drug Reporposing Strategy},
booktitle = {9th International Congress of the Molecular Biology Association of Turkey},
address = {İzmir},
year = {2024},
pages = {127},
url = {https://akademik.atauni.edu.tr/yayinlar/236132-in-silico-screening-of-new-delhi-metallo-v-lactamase-1ndm-1-inhibitors-with-drug}
}