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. 2022 Jul 18:10:949813.
doi: 10.3389/fchem.2022.949813. eCollection 2022.

Synthesis and Biological Evaluation of 3-(Pyridine-3-yl)-2-Oxazolidinone Derivatives as Antibacterial Agents

Bo Jin  1 , Tong Wang  1 , Jia-Yi Chen  1 , Xiao-Qing Liu  1 , Yi-Xin Zhang  1 , Xiu-Ying Zhang  1 , Zun-Lai Sheng  1   2 , Hong-Liang Yang  1   2
Affiliations

Synthesis and Biological Evaluation of 3-(Pyridine-3-yl)-2-Oxazolidinone Derivatives as Antibacterial Agents

Bo Jin et al. Front Chem. .

Abstract

In this research, a series of 3-(pyridine-3-yl)-2-oxazolidinone derivatives was designed, synthesized, and evaluated for in vitro antibacterial activity, which included bacteriostatic, morphological, kinetic studies, and molecular docking. The results demonstrated that compounds 21b, 21d, 21e and 21f exhibited strong antibacterial activity similar to that of linezolid toward five Gram-positive bacteria. After observing the effect of the drug on the morphology and growth dynamics of the bacteria, the possible modes of action were predicted by molecular docking. Furthermore, the antibiofilm activity and the potential drug resistance assay was proceeded. These compounds exhibited universal antibiofilm activity and compound 21d showed significant concentration-dependent inhibition of biofilm formation. Compound 21d also showed a stable effect on S. pneumoniae (ATCC 49619) with less drug resistance growth for 15 days, which is much longer than that of linezolid. Overall, these results can be used to guide further exploration of novel antimicrobial agents.

Keywords: 3-(pyridine-3-yl)-2-oxazolidinone; antibacterial activity; biofilm formation inhibitory activity; drug resistance development; molecular docking.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Optimization strategy of 3-(pyridine-3-yl)-2-oxazolidinone derivatives.
SCHEME 1
SCHEME 1
Synthesis of target compounds 9a-l.
SCHEME 2
SCHEME 2
Synthesis of target compounds 17a-l.
SCHEME 3
SCHEME 3
Synthesis of target compounds 21a-f.
FIGURE 2
FIGURE 2
SEM observation of S. pneumoniae ATCC 49619, before (A) and after treatment with 1/2 × MIC concentration of compounds 21b (B), 21d (C) and 21f (D).
FIGURE 3
FIGURE 3
SEM observation of S. aureus ATCC 25923, before (A) and after treatment with 1/2 × MIC concentration of compounds 21b (B), 21d (C) and 21f (D).
FIGURE 4
FIGURE 4
Time-growth kinetics for the compound 21d and linezolid (1/2 × MIC) against S. aureus (A), S. pneumoniae (B), E. faecalis (C) and S. xylosus (D) within 24 h.
FIGURE 5
FIGURE 5
Docking study: compound 17g (green) docked with ribosomal peptidyl transferase center (PTC) of 50S ribosomal subunit from Haloarcula marismortui (PDB ID: 3CPW). (A) compound 17g in an active pocket; (B) compound 17g docking with a nucleotide residue.
FIGURE 6
FIGURE 6
Docking study of compounds 21b (A), 21d (B), 21e (C) and 21f (D) with ribosomal peptidyl transferase center (PTC) of 50S ribosomal subunit from Haloarcula marismortui (PDB ID: 3CPW).
FIGURE 7
FIGURE 7
The influence of S. pneumoniae biofilm formation treated with 21d. Biofilm formation (O.D.600) of S. pneumoniae (ATCC 49619) in 96-well plates was quantified in the presence of 21d after 20 h. The error bar represents the standard error of the average calculated using data from at least three independent experiments.
FIGURE 8
FIGURE 8
The MIC variability of 21d and linezolid against S. pneumoniae (ATCC 49619) and Enterococcus faecalis (ATCC 29212) during 15 days of the resistance development assay, with linezolid as a comparison.
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References

    1. Anbarasi K., Esther Mary S., Vijayakumar R., Krishnan P. (2020). Resistance Profile and Minimum Inhibitory Concentration versus Minimum Biofilm Inhibitory Concentration of Biofilm Positive Staphylococci. Int. J. Infect. Dis. 101, 30. 10.1016/j.ijid.2020.09.113 - DOI
    1. Auckland C., Teare L., Cooke F., Kaufmann M., Warner M., Jones G., et al. (2002). Linezolid-resistant Enterococci: Report of the First Isolates in the United Kingdom. J. Antimicrob. Chemoth. 50, 743–746. 10.1093/jac/dkf246 - DOI - PubMed
    1. Bai P.-Y., Qin S.-S., Chu W.-C., Yang Y., Cui D.-Y., Hua Y.-G., et al. (2018). Synthesis and Antibacterial Bioactivities of Cationic Deacetyl Linezolid Amphiphiles. Eur. J. Med. Chem. 155, 925–945. 10.1016/j.ejmech.2018.06.054 - DOI - PubMed
    1. Brackman G., Risseeuw M., Celen S., Cos P., Maes L., Nelis H. J., et al. (2012). Synthesis and Evaluation of the Quorum Sensing Inhibitory Effect of Substituted Triazolyldihydrofuranones. Bioorg. Med. Chem. 20, 4737–4743. 10.1016/j.bmc.2012.06.009 - DOI - PubMed
    1. Brickner S. J., Barbachyn M. R., Hutchinson D. K., Manninen P. R. (2008). Linezolid (ZYVOX), the First Member of a Completely New Class of Antibacterial Agents for Treatment of Serious Gram-Positive Infections. J. Med. Chem. 51, 1981–1990. 10.1021/jm800038g - DOI - PubMed

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