Repurposing of Oxicam Derivatives to Inhibit NDM-1: Molecular Docking and Molecular Dynamic Simulation Studies
The New Delhi Metallo-β-lactamase-1 (NDM-1) causes hydrolysis of broad spectrum β-lactam antibiotics, such as carbapenems, resulting in the development of antimicrobial resistance. Still, there are not any approved NDM-1 inhibitors, globally. Therefore, repositioning approved medicines as NDM-1 inh...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
College of Pharmacy / Mustansiriyah University
2024-10-01
|
| Series: | Al-Mustansiriyah Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://ajps.uomustansiriyah.edu.iq/index.php/AJPS/article/view/1029 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850213166378647552 |
|---|---|
| author | Pshtiwan Gharib Ali Twana Mohsin Salih |
| author_facet | Pshtiwan Gharib Ali Twana Mohsin Salih |
| author_sort | Pshtiwan Gharib Ali |
| collection | DOAJ |
| description |
The New Delhi Metallo-β-lactamase-1 (NDM-1) causes hydrolysis of broad spectrum β-lactam antibiotics, such as carbapenems, resulting in the development of antimicrobial resistance. Still, there are not any approved NDM-1 inhibitors, globally. Therefore, repositioning approved medicines as NDM-1 inhibitors to combine with carbapenems may be a crucial strategy to combat resistant pathogens. This study repurposes.
Oxicam derivatives as inhibitors of bacterial NDM-1. The two-dimensional structures were obtained from the PubChem database. Twenty derivatives of oxicam were assessed computationally to realize their NDM-1 inhibition capability. To identify potential inhibitors of the NDM-1 target protein, a molecular docking protocol was used. In addition, drug-likeness and pharmacokinetic properties were predicted for the designed molecules. Three compounds with the most negative ΔGbinding results were chosen for additional study using molecular dynamic (MD) simulations. The compounds M010, M013, and M016 possessed a significantly more negative binding free energy than the positive control and other designed molecules, had stable MD simulations (Root-mean-square deviation < 0.5 Å), passed Lipinski's rule of five, and possessed favourable physicochemical and pharmacokinetic properties. The findings can inform In vitro studies of the promising compounds.
|
| format | Article |
| id | doaj-art-ddd1ed622db64ca880401f7cb03d08cd |
| institution | OA Journals |
| issn | 1815-0993 2959-183X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | College of Pharmacy / Mustansiriyah University |
| record_format | Article |
| series | Al-Mustansiriyah Journal of Pharmaceutical Sciences |
| spelling | doaj-art-ddd1ed622db64ca880401f7cb03d08cd2025-08-20T02:09:11ZengCollege of Pharmacy / Mustansiriyah UniversityAl-Mustansiriyah Journal of Pharmaceutical Sciences1815-09932959-183X2024-10-0124410.32947/ajps.v24i4.1029Repurposing of Oxicam Derivatives to Inhibit NDM-1: Molecular Docking and Molecular Dynamic Simulation StudiesPshtiwan Gharib Ali0Twana Mohsin Salih1Department of Pharmacognosy & Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, IraqDepartment of Pharmacognosy & Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Iraq The New Delhi Metallo-β-lactamase-1 (NDM-1) causes hydrolysis of broad spectrum β-lactam antibiotics, such as carbapenems, resulting in the development of antimicrobial resistance. Still, there are not any approved NDM-1 inhibitors, globally. Therefore, repositioning approved medicines as NDM-1 inhibitors to combine with carbapenems may be a crucial strategy to combat resistant pathogens. This study repurposes. Oxicam derivatives as inhibitors of bacterial NDM-1. The two-dimensional structures were obtained from the PubChem database. Twenty derivatives of oxicam were assessed computationally to realize their NDM-1 inhibition capability. To identify potential inhibitors of the NDM-1 target protein, a molecular docking protocol was used. In addition, drug-likeness and pharmacokinetic properties were predicted for the designed molecules. Three compounds with the most negative ΔGbinding results were chosen for additional study using molecular dynamic (MD) simulations. The compounds M010, M013, and M016 possessed a significantly more negative binding free energy than the positive control and other designed molecules, had stable MD simulations (Root-mean-square deviation < 0.5 Å), passed Lipinski's rule of five, and possessed favourable physicochemical and pharmacokinetic properties. The findings can inform In vitro studies of the promising compounds. https://ajps.uomustansiriyah.edu.iq/index.php/AJPS/article/view/1029Antibiotic resistancedrug repurposingmolecular dockingmolecular dynamics simulationNew Delhi Metallo-β-lactamase-1oxicam derivatives |
| spellingShingle | Pshtiwan Gharib Ali Twana Mohsin Salih Repurposing of Oxicam Derivatives to Inhibit NDM-1: Molecular Docking and Molecular Dynamic Simulation Studies Al-Mustansiriyah Journal of Pharmaceutical Sciences Antibiotic resistance drug repurposing molecular docking molecular dynamics simulation New Delhi Metallo-β-lactamase-1 oxicam derivatives |
| title | Repurposing of Oxicam Derivatives to Inhibit NDM-1: Molecular Docking and Molecular Dynamic Simulation Studies |
| title_full | Repurposing of Oxicam Derivatives to Inhibit NDM-1: Molecular Docking and Molecular Dynamic Simulation Studies |
| title_fullStr | Repurposing of Oxicam Derivatives to Inhibit NDM-1: Molecular Docking and Molecular Dynamic Simulation Studies |
| title_full_unstemmed | Repurposing of Oxicam Derivatives to Inhibit NDM-1: Molecular Docking and Molecular Dynamic Simulation Studies |
| title_short | Repurposing of Oxicam Derivatives to Inhibit NDM-1: Molecular Docking and Molecular Dynamic Simulation Studies |
| title_sort | repurposing of oxicam derivatives to inhibit ndm 1 molecular docking and molecular dynamic simulation studies |
| topic | Antibiotic resistance drug repurposing molecular docking molecular dynamics simulation New Delhi Metallo-β-lactamase-1 oxicam derivatives |
| url | https://ajps.uomustansiriyah.edu.iq/index.php/AJPS/article/view/1029 |
| work_keys_str_mv | AT pshtiwangharibali repurposingofoxicamderivativestoinhibitndm1moleculardockingandmoleculardynamicsimulationstudies AT twanamohsinsalih repurposingofoxicamderivativestoinhibitndm1moleculardockingandmoleculardynamicsimulationstudies |