Azole-Based Compounds That Are Active against Candida Biofilm: In Vitro, In Vivo and In Silico Studies

Carradori, S.; Ammazzalorso, A.; De Filippis, B.; Şahin, A.F.; Akdemir, A.; Orekhova, A.; andGiovanna Simonetti, G.B.

Авторы: Carradori Simone, Ammazzalorso Alessandra, De Filippis Barbara, Şahin Ahmet Fatih, Akdemir Atilla, Orekhova Anastasia, andGiovanna Simonetti Graziana Bonincontro
Журнал: Antibiotics
Год издания: 2022
Издательство: MDPI Publishing
Местоположение издательства: Basel, Switzerland, Switzerland
DOI: 10.3390/antibiotics11101375
Аннотация: first_pagesettingsOrder Article ReprintsOpen AccessArticleAzole-Based Compounds That Are Active against Candida Biofilm: In Vitro, In Vivo and In Silico Studiesby Simone Carradori 1,2ORCID,Alessandra Ammazzalorso 1,*ORCID,Barbara De Filippis 1ORCID,Ahmet Fatih Şahin 3,Atilla Akdemir 2,3ORCID,Anastasia Orekhova 4,Graziana Bonincontro 5 andGiovanna Simonetti 5ORCID1Department of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy2Computer-Aided Drug Discovery Laboratory, Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Istanbul, Turkey3Department of Drug Discovery and Development, Institute of Health Sciences, Bezmialem Vakif University, 34093 Istanbul, Turkey4Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00185 Rome, Italy5Department of Environmental Biology, “Sapienza” University of Rome, 00185 Rome, Italy*Author to whom correspondence should be addressed.Antibiotics 2022, 11(10), 1375; https://doi.org/10.3390/antibiotics11101375Received: 18 September 2022 / Revised: 3 October 2022 / Accepted: 3 October 2022 / Published: 8 October 2022(This article belongs to the Special Issue Design and Synthesis of Novel Antimicrobial Agents)Download Browse Figures Versions NotesAbstractFungal pathogens, including Candida spp., Aspergillus spp. and dermatophytes, cause more than a billion human infections every year. A large library of imidazole- and triazole-based compounds were in vitro screened for their antifungal activity against C. albicans, C. glabrata, C. krusei, A. fumigatus and dermatophytes, such as Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes. The imidazole carbamate 12 emerged as the most active compound, showing a valuable antifungal activity against C. glabrata (MIC 1–16 μg/mL) and C. krusei (MIC 4–24 μg/mL). No activity against A. fumigatus or the dermatophytes was observed among all the tested compounds. The compound 12 inhibited the formation of C. albicans, C. glabrata and C. krusei biofilms and reduced the mature Candida biofilm. In the Galleria mellonella larvae, 12 showed a significant reduction in the Candida infection, together with a lack of toxicity at the concentration used to activate its antifungal activity. Moreover, the in silico prediction of the putative targets revealed that the concurrent presence of the imidazole core, the carbamate and the p-chlorophenyl is important for providing a strong affinity for lanosterol 14α-demethylase (CgCYP51a1) and the fungal carbonic anhydrase (CgNce103), the S-enantiomer being more productive in these interactions.
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Azole-Based Compounds That Are Active against Candida Biofilm: In Vitro, In Vivo and In Silico Studiesстатья

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