Combined In Vitro and In Silico analysis of ferrocenylmethylaniline derivatives: Antibacterial potential, DFT calculations, and molecular dynamics insights

IF 2.1 3区化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR

Journal of Organometallic Chemistry Pub Date : 2025-03-23 DOI:10.1016/j.jorganchem.2025.123618

Yahia Bekkar , Elhafnaoui Lanez , Touhami Lanez , Lotfi Bourougaa , Aicha Adaika , Aida Benine , Zahra Saada

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引用次数: 0

Abstract

The rise of antimicrobial resistance poses a major public health threat by reducing the efficacy of treatments against infections in humans, animals, and plants. This study evaluates the antibacterial potential of three ferrocenylmethylaniline derivatives: Ferrocenylmethylaniline (FMA), N-Ferrocenylmethyl-N-acetylaniline (FMAA), and N-Ferrocenylmethyl-N-benzoylaniline (FMBA) against four clinically relevant bacterial strains (Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus aureus (S. aureus)). In vitro assays revealed FMBA as the most potent compound, with IC50 values of 26.18 mg/mL (E. coli), 34.33 mg/mL (P. aeruginosa), and 42.08 mg/mL (S. aureus), comparable to amoxicillin (AXL).

Molecular docking against twelve bacterial drug targets showed FMBA exhibited superior binding affinities, particularly with peptide deformylase, anthranilate-CoA ligase, peptidoglycan D,D-transpeptidase, dehydrosqualene synthase, and penicillin-binding protein 2a . DFT analysis, including thermodynamic parameters and non-covalent interactions (Reduced Density Gradient, Electron Localization Function, Localized Orbital Locator), provided deeper insights into electronic structures, stability, and binding interactions. Molecular dynamics simulations confirmed the stability of FMBA-protein complexes, reinforcing its potential as a promising antimicrobial lead compound. These findings suggest FMBA as a strong candidate for the development of novel antibacterial agents targeting drug-resistant pathogens.

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来源期刊

Journal of Organometallic Chemistry 化学-无机化学与核化学

CiteScore

4.40

自引率

8.70%

发文量

221

审稿时长

36 days

期刊介绍： The Journal of Organometallic Chemistry targets original papers dealing with theoretical aspects, structural chemistry, synthesis, physical and chemical properties (including reaction mechanisms), and practical applications of organometallic compounds. Organometallic compounds are defined as compounds that contain metal - carbon bonds. The term metal includes all alkali and alkaline earth metals, all transition metals and the lanthanides and actinides in the Periodic Table. Metalloids including the elements in Group 13 and the heavier members of the Groups 14 - 16 are also included. The term chemistry includes syntheses, characterizations and reaction chemistry of all such compounds. Research reports based on use of organometallic complexes in bioorganometallic chemistry, medicine, material sciences, homogeneous catalysis and energy conversion are also welcome. The scope of the journal has been enlarged to encompass important research on organometallic complexes in bioorganometallic chemistry and material sciences, and of heavier main group elements in organometallic chemistry. The journal also publishes review articles, short communications and notes.