4-Trifluoromethyl bithiazoles as broad-spectrum antimicrobial agents for virus-related bacterial infections or co-infections
Respiratory tract infections involving a variety of microorganisms such as viruses, bacteria, and fungi are a prominent cause of morbidity and mortality globally, exacerbating various pre-existing respiratory and non-respiratory conditions. Moreover, the ability of bacteria and viruses to coexist mi...
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Published in | MedChemComm Vol. 15; no. 5; pp. 1589 - 16 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
CAMBRIDGE
Royal Soc Chemistry
22.05.2024
Royal Society of Chemistry |
Subjects | |
Online Access | Get full text |
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Summary: | Respiratory tract infections involving a variety of microorganisms such as viruses, bacteria, and fungi are a prominent cause of morbidity and mortality globally, exacerbating various pre-existing respiratory and non-respiratory conditions. Moreover, the ability of bacteria and viruses to coexist might impact the development and severity of lung infections, promoting bacterial colonization and subsequent disease exacerbation. Secondary bacterial infections following viral infections represent a complex challenge to be overcome from a therapeutic point of view. We report herein our efforts in the development of new bithiazole derivatives showing broad-spectrum antimicrobial activity against both viruses and bacteria. A series of 4-trifluoromethyl bithiazole analogues was synthesized and screened against selected viruses (hRVA16, EVD68, and ZIKV) and a panel of Gram-positive and Gram-negative bacteria. Among them, two promising broad-spectrum antimicrobial compounds (
8a
and
8j
) have been identified: both compounds showed low micromolar activity against all tested viruses,
8a
showed synergistic activity against
E. coli
and
A. baumannii
in the presence of a subinhibitory concentration of colistin, while
8j
showed a broader spectrum of activity against Gram-positive and Gram-negative bacteria. Activity against antibiotic-resistant clinical isolates is also reported. Given the ever-increasing need to adequately address viral and bacterial infections or co-infections, this study paves the way for the development of new agents with broad antimicrobial properties and synergistic activity with common antivirals and antibacterials.
Is magic trifluoromethyl a thing? Replacing 4-CH
3
with 4-CF
3
in bithiazoles, allowed to identify broad antimicrobial agents active against multiple viruses and also against Gram-positive/negative bacteria. |
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Bibliography: | Electronic supplementary information (ESI) available: NMR spectra of final compounds. See DOI https://doi.org/10.1039/d3md00686g ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2632-8682 2040-2503 2632-8682 2040-2511 |
DOI: | 10.1039/d3md00686g |