Thiazole Derivatives as Promising Candidates for Cryptococcosis Therapy
Cryptococcosis is a severe fungal infection primarily caused by two encapsulated yeasts: <i>Cryptococcus neoformans</i> and <i>C. gattii</i>. The most significant complication is cryptococcal meningitis, where the fungus crosses the blood-brain barrier, leading to a severe brain infection. Current treatments, which include amphotericin B and flucytosine or fluconazole, are often toxic and not very effective. Therefore, there is a pressing need for new antifungal agents. This study screened 30 thiazole derivatives for their antifungal activity against <i>Cryptococcus</i> and their toxicity to brain cells. Four compounds (RN86, RN88, RJ37, and RVJ42) showed particularly strong effects. These compounds reduced ergosterol levels in the fungal membrane and inhibited its ability to cross the blood-brain barrier. Notably, RN86 and RVJ42 improved survival rates in a mouse model of cryptococcosis by lowering the fungal load in the lungs and brain. These findings suggest that these derivatives could be promising treatments for pulmonary and neurocryptococcosis.
Authors
- Daniel Assis Santos (ORCID: https://orcid.org/0000-0002-1108-5666)
- José Eduardo Gonçalves (ORCID: https://orcid.org/0000-0002-2505-0536)
- Renata Barbosa de Oliveira (ORCID: https://orcid.org/0000-0001-5884-2567)
- Gustavo H. Goldman (ORCID: https://orcid.org/0000-0002-2986-350X)
- Vinícius Gonçalves Maltarollo (ORCID: https://orcid.org/0000-0001-9675-5907)
- Nalu Teixeira de Aguiar Peres (ORCID: https://orcid.org/0000-0003-2762-3200)
- Victor Augusto Teixeira Leocádio (ORCID: https://orcid.org/0000-0002-0260-353X)
- Susana Johann (ORCID: https://orcid.org/0000-0001-8068-1720)
- Valtair Severino dos Santos (ORCID: https://orcid.org/0000-0002-4291-8624)
- Martha Helena Chaves Magalhães
- Rafael Wesley Bastos (ORCID: https://orcid.org/0000-0001-6781-9617)
- Ismael Miranda
Institutions
- Universidade Federal de Minas Gerais (BR)
- Universidade de São Paulo (BR)
- Universidade Federal do Rio Grande do Norte (BR)
- Instituto de Ciências Farmacêuticas (BR)
- Colciencias (CO)
- National Institute of Science and Technology (ID)
Publication Details
- Journal
- ACS Infectious Diseases
- Published
- 2025-02-07
- DOI
- https://doi.org/10.1021/acsinfecdis.4c00732
- Citations
- 6
- Primary Topic
- Fungal Infections and Studies
- Type
- article
- Field-Weighted Citation Impact
- 8.13
Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico