Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 70, Issue 3, Pages 841-845Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dku427
Keywords
paracoccidioidomycosis; murine model; morphological changes
Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo Pesquisa Estado de Minas Gerais (FAPEMIG)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
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Background: Chalcones are an important class of natural compounds that have been widely applied as synthons in synthetic organic chemistry and possess diverse and interesting biological properties. Methods: We conducted tests with the synthetic substances 6-quinolinyl N-oxide chalcones 4c and 4e to determine their antifungal activity against several isolates of Paracoccidioides spp. and their activity in a murine model. We also determined whether the chalcones interacted with other drugs or interfered with the morphology of Paracoccidioides brasiliensis (Pb18) yeast cells. Results: We verified that the substances were active against Paracoccidioides spp., but we did not show an interaction with the drugs tested when only the fractional inhibitory concentration index values were considered individually. We observed that the substances induced in vitro morphological changes. Compounds 4c and 4e showed activity similar to itraconazole in treated mice, as demonstrated by their ability to reduce the number of cfu recovered from the lungs. Histopathological analysis showed that animals treated with 4c presented fewer areas containing inflammatory infiltrate and larger areas of preserved lung tissue, whereas animals treated with itraconazole showed accumulation of inflammatory infiltrate and some granulomas. Mice treated with 4e exhibited inflammation that compromised the tissue. Conclusions: The results presented in this paper confirm the antifungal potential of the chalcones tested. The chalcone 4c was the more effective at controlling the disease in mice and this compound could be a candidate for future studies of the treatment of paracoccidioidomycosis.
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