In Silico Design and Molecular Docking Studies of Carbapenem Analogues Targeting Acinetobacter baumannii PBP1A Receptor

Salih, Twana; Salih, Hawzhin A.

doi:10.32947/ajps.v20i3.759

Cited by 6 publications

References 57 publications

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Rational design of novel compounds to serve as potential NDM-1 inhibitors using molecular docking, molecular dynamics simulation, and physicochemical studies

Salih

Ali

2023

Preprint

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New Delhi Metallo-β-lactamase enzyme (NDM-1) is an enzyme that hydrolyzes a wide range of β-lactam antibiotics, including most carbapenems, leading to antimicrobial resistance. The development of a novel NDM-1 inhibitor for use in combination with carbapenems may help to combat drug-resistant pathogens. Twenty compounds derived from naphthalene, thiazole, and sulfone derivatives were designed to inhibit bacterial NDM-1 and protect β-lactam antibiotics from enzyme attack. Two- and three-dimensional structures of the designed molecules were sketched using MarvinSketch, and a molecular docking protocol was used to identify potential inhibitor(s) of the NDM-1 target protein using AMDock v 1.5.2. The binding free energy of each compound against NDM-1 was determined and the drug-likeness properties of the designed molecules were assessed using SwissADME. Two compounds with the highest ΔGbinding results, T008 and T016, were selected for further investigation using molecular dynamic (MD) simulations with the GROMACS simulation package (GROMACS 2020.4). The duration of each MD simulation was 100 ns. Both compounds had a significantly higher binding free energy than the positive control and other designed molecules, their MD simulations remained stable, they passed Lipinski’s rule of five, and were shown to have favorable physicochemical properties. The study outcomes can be used to inform synthesis and in vitro testing of the selected molecules.

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Rational design of novel compounds to serve as potential NDM-1 inhibitors using molecular docking, molecular dynamics simulation, and physicochemical studies

Salih

Ali

2023

Preprint

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Design, Synthesis, and Anti-Inflammatory Activity of Some Coumarin Schiff Base Derivatives: In silico and in vitro Study

Hamid¹,

Salih²

2022

DDDT

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Introduction Inflammation is a fundamental response of the immune system during tissue damage or pathogen infection to protect and maintain tissue homeostasis. However, inflammation may lead to life-threatening conditions. The most common treatment of inflammation is non-steroidal anti-inflammatory drugs (NSAIDs). Nowadays, the development of safer new NSAIDs is critical as most of the existing NSAIDs have serious adverse effects, such as gastrointestinal (GI) toxicity and cardiotoxicity. In the present study, four compounds as Schiff base derivatives of 7-hydroxy-4-formyl coumarin and 7-methoxy-4-formyl coumarin were designed and synthesized aiming to develop a lead compound that exhibits anti-inflammatory activity and circumvents the side effects of NSAIDs, especially GI toxicity. Materials and Methods Lipinski’s rule of five was applied for each designed molecule to evaluate the drug-likeness properties. Molecular docking studies were performed using the ligands and the cyclooxygenase-2 (COX-2) protein to select the best-scored molecule using AutoDock 4.2.6. The molecules were then synthesized and characterized. An in vitro anti-inflammatory assay of the compounds against the COX-2 receptor was realized through a protein denaturation assay. Results and Discussion All four synthesized ligands passed Lipinski’s rule of five and exhibited higher binding free energy compared to the positive standard control (ibuprofen), and the K i values of compounds 5, 7, and 8 were in the nanomolar range. However, only compounds 6 and 7 obtained a higher percentage of inhibition of protein denaturation relative to ibuprofen. Conclusion The present study suggested that compound 7 may be a lead molecule because this ligand not only exhibited the best computational and experimental results but also exhibited the strongest correlation between the concentration and percentage of protein denaturation (R = 0.986 and R 2 = 0.972) with the lowest P-value (0.014).

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Characterization, antibacterial and antibiofilm evaluation of biosynthesized silver nanoparticles from Pseudomonas aeruginosa against drug resistant Acinetobacter baumannii

Hasan

Ahmed

2023

AJPS

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Antimicrobial resistance is regarded as one of the top three terrible events threatening the worldwide existence of humans Here of, Acinetobacter baumannii evolved as the most challenging pathogen threatening to initiate the post-antibiotic era. Their ability to withstand antibiotics is attributed to a set of virulence determinants in particular biofilms which are known to enhance pathogenesis and drug resistance potency. Studies regarding green silver nanoparticles (AgNP)s as an alternative treatment modality to antibiotics increased over recent years. Considering these facts, we aimed to explore the antibiofilm effect of AgNPs in the multi-drug-resistant Acinetobacter baumannii. AgNPs were bio-fabricated by Pseudomonas aeruginosa and characterized via FTIR, UV-Vis, XRD, EDS, and SEM. Well-diffusion was used to screen the antimicrobial effects of AgNPs. Minimal-inhibitory concentrations of AgNPs were determined to study their antibiofilm effect at sub-inhibitory concentrations (SIC). Results showed that all isolates were biofilm producers and portrayed high resistance to the tested antibiotics. Characterization results supported the successful fabrication of crystalline nanoparticles. Exposure of the isolates to the bacteriogenic AgNPs resulted in pronounced inhibition zones and reduced biofilms at SICs values. These results indicate that Pseudomonas aeruginosa can be employed to produce AgNPs with an aptitude to disrupt biofilm development and growth in the multi-drug resistant Acinetobacter baumannii.

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In Silico Design and Molecular Docking Studies of Carbapenem Analogues Targeting Acinetobacter baumannii PBP1A Receptor

Cited by 6 publications

References 57 publications

Rational design of novel compounds to serve as potential NDM-1 inhibitors using molecular docking, molecular dynamics simulation, and physicochemical studies

Rational design of novel compounds to serve as potential NDM-1 inhibitors using molecular docking, molecular dynamics simulation, and physicochemical studies

Design, Synthesis, and Anti-Inflammatory Activity of Some Coumarin Schiff Base Derivatives: In silico and in vitro Study

Characterization, antibacterial and antibiofilm evaluation of biosynthesized silver nanoparticles from Pseudomonas aeruginosa against drug resistant Acinetobacter baumannii

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