Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro
| Autor: | Elaine M. Souza-Fagundes, Susana Johann, Renata Barbosa de Oliveira, Carlos A. Rosa, Nayara Cristina Fonseca, Nívea Pereira de Sá, Beatriz M. Borelli, Daniel Assis Santos, Jonas Pereira Ramos, Cleudiomar Inácio Lino |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Antifungal Agents
Cryptococcus Microbial Sensitivity Tests Microbiology Mice Structure-Activity Relationship chemistry.chemical_compound Amphotericin B Chlorocebus aethiops Drug Discovery medicine Animals Cytotoxicity Vero Cells Cryptococcus gattii Pharmacology Cryptococcus neoformans Ergosterol Dose-Response Relationship Drug Molecular Structure biology Macrophages Organic Chemistry General Medicine bacterial infections and mycoses medicine.disease biology.organism_classification Thiazoles chemistry Cryptococcosis Fluconazole medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 102:233-242 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2015.07.032 |
| Popis: | Human cryptococcosis can occur as a primary or opportunistic infection and develop as an acute, subacute, or chronic, systemic infection involving different host organs. We evaluated the antifungal activity of thirteen compounds against Cryptococcus gattii and Cryptococcus neoformans in vitro, by assessing the toxicity of the compounds showing the greatest antifungal activity in VERO cells and murine macrophages. From these results, four compounds were considered promising for further studies because they displayed low cytotoxicity and significant antifungal activity. The heterocyclic compounds 1b, 1c, 1d, and 1m have antifungal activity levels between that of amphotericin B and fluconazole in vitro. The death curve of Cryptococcus spp. treated with these four compounds was similar to the curve obtained for amphotericin B, in that we observed a significant reduction in cell viability within the first 24 h of treatment. Additionally, we found that there was no effect when these compounds were combined with amphotericin and fluconazole, except for 1c, which antagonized the effect of amphotericin B against C. gattii, also reflected in the reduction of the post-antifungal effect (PAFE); however, this interaction did not alter the ergosterol content. The results shown in this paper reveal the discovery of novel thiazole compounds, which are easy to synthesize, and with potentially exhibit antifungal activity, and display low cytotoxicity in normal mammalian cells. These compounds can be used as prototypes for the design of new antifungal drugs against C. gattii and C. neoformans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect