title: Novel Macrocyclic Amidinoureas: Potent Non-Azole Antifungals Active against Wild-Type and Resistant Candida Species.
abstract: Novel macrocyclic amidinourea derivatives 11, 18, and 25 were synthesized and evaluated as antifungal agents against wild-type and fluconazole resistant Candida species. Macrocyclic compounds 11 and 18 were synthesized through a convergent approach using as a key step a ring-closing metathesis macrocyclization reaction, whereas compounds 25 were obtained by our previously reported synthetic pathway. All the macrocyclic amidinoureas showed antifungal activity toward different Candida species higher or comparable to fluconazole and resulted highly active against fluconazole resistant Candida strains showing in many cases minimum inhibitory concentration values lower than voriconazole.
authors.affiliation: Istituto di Microbiologia, Università Cattolica del Sacro Cuore , Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università di Siena , via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sanfilippo
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università di Siena , via Aldo Moro 2, 53100 Siena, Italy ; School of Applied Sciences, Northumbria University , Ellison Building, Ellison Place, NE1 8ST, Newcastle upon Tyne, United Kingdom.
authors.forename: Daniele
authors.initials: D
authors.lastname: Castagnolo
authors.affiliation: Institute of Microbiology, University of Lausanne and University Hospital Center , Lausanne, Rue du Bugnon 48, CH-1011 Lausanne, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
authors.affiliation: Istituto di Microbiologia, Università Cattolica del Sacro Cuore , Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Posteraro
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università di Siena , via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Donzellini
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università di Siena , via Aldo Moro 2, 53100 Siena, Italy ; Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University , BioLife Science Building, Suite 333, 1900 North 12th Street, Philadelphia, Pennsylvania 19122, United States.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
keywords: Antifungal; Candida species; amidinourea; antifungal drug-resistance; fluconazole; macrocyclization; ring-closing metathesis