Focused library of phenyl-fused macrocyclic amidinoureas as antifungal agents.
Mol Divers
; 26(6): 3399-3409, 2022 Dec.
Article
in English
| MEDLINE | ID: covidwho-1681346
ABSTRACT
The rise of antimicrobial-resistant phenotypes and the spread of the global pandemic of COVID-19 are worsening the outcomes of hospitalized patients for invasive fungal infections. Among them, candidiases are seriously worrying, especially since the currently available drug armamentarium is extremely limited. We recently reported a new class of macrocyclic amidinoureas bearing a guanidino tail as promising antifungal agents. Herein, we present the design and synthesis of a focused library of seven derivatives of macrocyclic amidinoureas, bearing a second phenyl ring fused with the core. Biological activity evaluation shows an interesting antifungal profile for some compounds, resulting to be active on a large panel of Candida spp. and C. neoformans. PAMPA experiments for representative compounds of the series revealed a low passive diffusion, suggesting a membrane-based mechanism of action or the involvement of active transport systems. Also, compounds were found not toxic at high concentrations, as assessed through MTT assays.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cryptococcus neoformans
/
COVID-19
Type of study:
Experimental Studies
Language:
English
Journal:
Mol Divers
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
S11030-022-10388-7
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