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.

Balestri, L.J.I., D'Agostino, I., Rango, E., Vagaggini, C., Marchitiello, R., Mariotti, M., et al. (2022). Focused library of phenyl-fused macrocyclic amidinoureas as antifungal agents. MOLECULAR DIVERSITY [10.1007/s11030-022-10388-7].

Focused library of phenyl-fused macrocyclic amidinoureas as antifungal agents

Ilaria D’Agostino;Enrico Rango;Chiara Vagaggini;Alexandru Casian;Davide Deodato;Giuseppina I. Truglio;Francesco Orofino;Lorenzo Botta
Data Curation
;
Elena Dreassi
Data Curation
2022-01-01

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.
Balestri, L.J.I., D'Agostino, I., Rango, E., Vagaggini, C., Marchitiello, R., Mariotti, M., et al. (2022). Focused library of phenyl-fused macrocyclic amidinoureas as antifungal agents. MOLECULAR DIVERSITY [10.1007/s11030-022-10388-7].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1216899
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