2. Academic Validation
  3. Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro

Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro

  • Eur J Med Chem. 2015 Sep 18:102:233-42. doi: 10.1016/j.ejmech.2015.07.032.
Nívea Pereira de Sá 1,  Cleudiomar Inácio Lino 2,  Nayara Cristina Fonseca 2,  Beatriz Martins Borelli 1,  Jonas Pereira Ramos 3,  Elaine Maria Souza-Fagundes 3,  Carlos Augusto Rosa 1,  Daniel Assis Santos 1,  Renata Barbosa de Oliveira 2,  Susana Johann 4
Affiliations

Affiliations

  • 1 Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 2 Departamento de Produtos Farmacêuticos, Faculdade de Farmácia da UFMG, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 3 Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 4 Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: [email protected].
PMID: 26276437 DOI: 10.1016/j.ejmech.2015.07.032
Abstract

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.

Keywords

Antifungal; Cryptococcus; Cytotoxicity; Thiazole.

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