Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 15;25(12):2758.
doi: 10.3390/molecules25122758.

Synthesis and Antimicrobial Studies of Coumarin-Substituted Pyrazole Derivatives as Potent Anti- Staphylococcus aureus Agents

Rawan Alnufaie  1 , Hansa Raj Kc  1 , Nickolas Alsup  1 , Jedidiah Whitt  1 , Steven Andrew Chambers  1 , David Gilmore  2 , Mohammad A Alam  1
Affiliations

Synthesis and Antimicrobial Studies of Coumarin-Substituted Pyrazole Derivatives as Potent Anti- Staphylococcus aureus Agents

Rawan Alnufaie et al. Molecules. .

Abstract

In this paper, synthesis and antimicrobial studies of 31 novel coumarin-substituted pyrazole derivatives are reported. Some of these compounds have shown potent activity against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) as low as 3.125 µg/mL. These molecules are equally potent at inhibiting the development of MRSA biofilm and the destruction of preformed biofilm. These results are very significant as MRSA strains have emerged as one of the most menacing pathogens of humans and this bacterium is bypassing HIV in terms of fatality rate.

Keywords: MRSA; S. epidermidis; Staphylococcus aureus; antimicrobial; biofilm; coumarin; hydrazone; pyrazole.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative examples of medicinally important pyrazole and coumarin derivatives.
Scheme 1
Scheme 1
Synthesis of coumarin-substituted pyrazole-derived aldehyde.
Scheme 2
Scheme 2
Synthesis of coumarin-substituted pyrazole-derived hydrazones.
Figure 2
Figure 2
Representation of the biofilm inhibitory (a) and destructive capacity (b) of the active compounds against S. aureus ATCC 25923. Inhibition values are in percentage.
Figure 3
Figure 3
Time kill assay. Compounds were tested at 4 × MIC (except indicated) against (a) A. baumannii ATCC 19606 and (b) S. aureus ATCC 33599 (MRSA) over an incubation period of 24 h at 35 oC.
Figure 4
Figure 4
Cytotoxicity assay of potent compounds 7, 12, 13, and 19 against HEK293 cells.
See this image and copyright information in PMC

References

    1. WHO New Report Calls for Urgent Action to Avert Antimicrobial Resistance Crisis. [(accessed on 28 February 2020)]; Available online: https://www.who.int/news-room/detail/29-04-2019-new-report-calls-for-urg....
    1. CDC Antibiotic/Antimicrobial Resistance (AR/AMR) [(accessed on 28 February 2020)]; Available online: https://www.cdc.gov/drugresistance/biggest-threats.html.
    1. Craft K.M., Nguyen J.M., Berg L.J., Townsend S.D. Methicillin-resistant Staphylococcus aureus (MRSA): Antibiotic-resistance and the biofilm phenotype. Med. Chem. Comm. 2019;10:1231–1241. doi: 10.1039/C9MD00044E. - DOI - PMC - PubMed
    1. Alam M.J., Alam O., Khan S.A., Naim M.J., Islamuddin M., Deora G.S. Synthesis, anti-inflammatory, analgesic, COX1/2-inhibitory activity, and molecular docking studies of hybrid pyrazole analogues. Drug Des. Devel. Ther. 2016;10:3529–3543. doi: 10.2147/DDDT.S118297. - DOI - PMC - PubMed
    1. Driscoll J.P., Sadlowski C.M., Shah N.R., Feula A. Metabolism and Bioactivation: It’s Time to Expect the Unexpected. J. Med. Chem. 2020 doi: 10.1021/acs.jmedchem.0c00026. - DOI - PubMed

MeSH terms

LinkOut - more resources