دورية أكاديمية
أعرض في EDS

Molecular Modelling Study and Antibacterial Evaluation of Diphenylmethane Derivatives as Potential FabI Inhibitors.

التفاصيل البيبلوغرافية
العنوان: Molecular Modelling Study and Antibacterial Evaluation of Diphenylmethane Derivatives as Potential FabI Inhibitors.
المؤلفون: Hasan S; College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates., Kayed K; College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates.; AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates., Ghemrawi R; College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates.; AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates., Bataineh NA; College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates.; AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates., Mahgoub RE; AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates., Audeh R; College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates., Aldulaymi R; AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates., Atatreh N; College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates.; AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates., Ghattas MA; College of Pharmacy, Al Ain University, Abu Dhabi 64141, United Arab Emirates.; AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 64141, United Arab Emirates.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2023 Mar 28; Vol. 28 (7). Date of Electronic Publication: 2023 Mar 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Anti-Bacterial Agents*/pharmacology , Anti-Bacterial Agents*/chemistry , Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)*/metabolism, Gram-Negative Bacteria/metabolism ; Enzyme Inhibitors/pharmacology ; Gram-Positive Bacteria/metabolism ; Bacteria/metabolism ; Molecular Dynamics Simulation
مستخلص: The need for new antibiotics has become a major worldwide challenge as bacterial strains keep developing resistance to the existing drugs at an alarming rate. Enoyl-acyl carrier protein reductases (FabI) play a crucial role in lipids and fatty acid biosynthesis, which are essential for the integrity of the bacterial cell membrane. Our study aimed to discover small FabI inhibitors in continuation to our previously found hit MN02. The process was initially started by conducting a similarity search to the NCI ligand database using MN02 as a query. Accordingly, ten compounds were chosen for the computational assessment and antimicrobial testing. Most of the compounds showed an antibacterial activity against Gram-positive strains, while RK10 exhibited broad-spectrum activity against both Gram-positive and Gram-negative bacteria. All tested compounds were then docked into the saFabI active site followed by 100 ns MD simulations (Molecular Dynamics) and MM-GBSA (Molecular Mechanics with Generalised Born and Surface Area Solvation) calculations in order to understand their fitting and estimate their binding energies. Interestingly, and in line with the experimental data, RK10 was able to exhibit the best fitting with the target catalytic pocket. To sum up, RK10 is a small compound with leadlike characteristics that can indeed act as a promising candidate for the future development of broad-spectrum antibacterial agents.
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فهرسة مساهمة: Keywords: FabI; antimicrobial activity; diphenyl methane; docking; enoyl-acyl carrier protein transferase; lead optimization; molecular dynamic simulation; triclosan
المشرفين على المادة: 0 (Anti-Bacterial Agents)
K3E387I0BC (diphenylmethane)
EC 1.3.1.9 (Enoyl-(Acyl-Carrier-Protein) Reductase (NADH))
0 (Enzyme Inhibitors)
تواريخ الأحداث: Date Created: 20230413 Date Completed: 20230414 Latest Revision: 20230415
رمز التحديث: 20230415
مُعرف محوري في PubMed: PMC10095751
DOI: 10.3390/molecules28073000
PMID: 37049763
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules28073000