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. 2024 Sep 6;10(17):e37538.
doi: 10.1016/j.heliyon.2024.e37538. eCollection 2024 Sep 15.

Insights into bacterial interactions: Comparing fluorine-containing 1,2,4-triazoles to antibiotics using molecular docking and molecular dynamics approaches

Affiliations

Insights into bacterial interactions: Comparing fluorine-containing 1,2,4-triazoles to antibiotics using molecular docking and molecular dynamics approaches

Nataliya Korol et al. Heliyon. .

Abstract

Understanding the interactions between drugs and enzymes is crucial for designing effective therapeutics. This study employed a combination of molecular docking and molecular dynamics (MD) simulations to evaluate the binding affinity, stability, and dynamic behavior of two new compounds (compound 1 and compound 2) compared to vancomycin and meropenem against Staphylococcus aureus and Serratia marcescens bacterial enzymes. Molecular docking studies provided insights into the binding interactions and affinities of these compounds, revealing that both compound 1 and compound 2 exhibit promising binding profiles. In particular, compound 1 demonstrated lower binding energies with key enzymes from Staphylococcus aureus compared to vancomycin, suggesting enhanced potential. MD simulations further elucidated the dynamic stability of these complexes. Results indicated that compound 1 maintains consistent binding modes with low RMSD and RMSF values, implying stable interactions. In contrast, vancomycin exhibited high RMSD and RMSF values in some enzyme complexes, reflecting potential instability. Compound 2 showed competitive stability and binding behavior compared to meropenem, with comparable RMSD and RMSF values across various enzyme targets. These findings highlight the potential of compound 1 and compound 2 as viable candidates for further development, offering insights into their stability and efficacy as new therapeutic agents.

Keywords: 1,2,4-Triazol-3-thione; Bactericide; Molecular docking; Molecular dynamics; Serratia marcescens; Staphylococcus aureus; per-fluoralkyl.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Molecular formulas of investigated compounds.
Fig. 2
Fig. 2
Physicochemical properties of compound 1 (left) and compound 2 (right) are presented. The properties are as follows: molecular weight (MW), number of rings (nRig), formal charge (fChar), number of heteroatoms (nHet), number of atoms in the biggest ring (MaxRing), number of rigid bonds (nRing), number of rotatable bonds (nRot), topological polar surface area (TPSA), number of hydrogen bond donors (nHD), number of hydrogen bond acceptors (nHA), logarithm of the n-octanol/water distribution coefficients at pH 7.4 (LogD), logarithm of aqueous solubility value (LogS), and logarithm of the n-octanol/water distribution coefficient (LogP). The central blue lines represent the properties of the compounds, fitting within the pink area, which indicates the optimal range for each property.
Fig. 3
Fig. 3
Ramachandran plots for 1BQB (left) and 6ZZ5 (right).
Fig. 4
Fig. 4
2D (left) and 3D (right) visualization of the interaction between Tyrosyl-tRNA synthetase of Staphylococcus aureus (PDB ID: 1JIJ) and compound 1.
Fig. 5
Fig. 5
3D visualization of the interaction between Tyrosyl-tRNA synthetase of Staphylococcus aureus (PDB ID: 1JIJ) and vancomycin.
Fig. 6
Fig. 6
2D representation of interactions between 1I7S with compond 2 (left) and meropenem (right).
Fig. 7
Fig. 7
RMSF curve for complexes of Aureolysin with compound 1 and vancomycin.
Fig. 8
Fig. 8
RMSF curve for complexes of Symmetrical Tetramer of Staphylococcus aureus Pyruvate Carboxylase with compound 1 and vancomycin.

References

    1. Frieri M., Kumar K., Boutin A. Antibiotic resistance. J. Infect. Public Health. 2017;10:369–378. doi: 10.1016/j.jiph.2016.08.007. - DOI - PubMed
    1. Mancuso G., Midiri A., Gerace E., Biondo C. Bacterial antibiotic resistance: the most critical pathogens. Pathogens. 2021;10:1310–1324. doi: 10.3390/pathogens10101310. - DOI - PMC - PubMed
    1. Nwobodo D.C., Ugwu M.C., Anie O.C., Al-Ouqaili M.T.S., Ikem J.C., Chigozie U.V., Saki M. Antibiotic resistance: the challenges and some emerging strategies for tackling a global menace. J. Clin. Lab. Anal. 2022;36 doi: 10.1002/jcla.24655. - DOI - PMC - PubMed
    1. Urban-Chmiel R., Marek A., Stępień-Pyśniak D., Wieczorek K., Dec M., Nowaczek A., Osek J. Antibiotic resistance in bacteria — a review. Antibiotics. 2022;11:1079–1119. doi: 10.3390/antibiotics11081079. - DOI - PMC - PubMed
    1. Rusu A., Moga I.-M., Uncu L., Hancu G. The role of five-membered heterocycles in the molecular structure of antibacterial drugs used in therapy. Pharmaceutic. 2023;15:2554–2605. doi: 10.3390/pharmaceutics15112554. - DOI - PMC - PubMed

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