In vitro studies of anticandidal activity of goniothalamin enantiomers

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Aims: The antifungal activity of (R)-goniothalamin (1) and (S)-goniothalamin (ent-1) was evaluated against six Candida species. The in vitro effect of these compounds on yeast adhesion to human buccal epithelial cells (BEC) and Candida albicans and C. dubliniensis biofilms progression were also investigated. Methods and Results: Yeast susceptibility was evaluated by broth microdilution assay and showed that ent-1 exhibited higher potency against all fungal clinical isolated when compared to compound 1. Compounds 1 and ent-1 were as potent as fluconazole in inhibiting the adhesion of C. albicans and C. dubliniensis to BEC. XTT-reducing assay and scanning electron microscopy revealed that 1 and ent-1 were twice as potent as fluconazole in the inhibition of yeast biofilms progression. Conclusions: Our findings indicate that compounds 1 and ent-1 are potent anticandidal agents. Significance and Impact of the Study: This study highlights goniothalamin enantiomers as promising lead compounds for the design of new antifungal with inhibitory activity on yeast adhesion and biofilm progression.107412791286Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Antifungal activity of goniothalamin enantiomers

A large number of human diseases are caused by fungus and the plant kingdom has proven to be a source of antifungal compounds. This work describes the in vitro activity of the natural product (R)-goniothalamin and its synthetic enantiomer, (S)-goniothalamin, against eleven strains of human pathogenic fungi. The minimum inhibitory concentration (MIC) values for both enantiomers were lower than 100 mu g/mL for nine of the fungus strains studied. MIC values for both enantiomers against isolates of the dimorphic fungus Paracoccidioides braziliensis were in the range of 7-22 mu g/mL. (R)- and (S)-goniothalamin were selective for the fungi strains presenting minimal toxic effects on mammalian kidney (Vero) and lung (V79) cell lines.51747

Antiproliferative and Antifungal Activities of 1,3-diarylpropane-1,3-diones Commonly used as Sunscreen Agents

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Parsol 1789 and eusolex 8021 are two 1,3-diarylpropane-1,3-diones widely used as UV-absorbing agents in sunscreen formulations. Their chemical structures are quite similar to that of curcumin, a natural compound known to present a wide range of relevant pharmacological activities, including antifungal and anticancer activities. Such structural similarity, together with their availability and low cost sparked our interest for investigating their potential as antiproliferative and antifungal agents. Parsol and eusolex presented antiproliferative activity against eight human cancer cell lines. Promisingly, parsol was almost as active against the human lung cancer cell line NCI-ADR/RES (GI(50) 1.1 +/- 0.8 mu g mL(-1)) as the positive control doxorubicin (GI(50) 1.7 +/- 2.1 mu g mL(-1)). When tested for antifungal activity, parsol and eusolex showed activity comparable to that of fluconazole, the reference drug, against Paracoccidioides brasiliensis and Cryptococcus neoformans. Sporothrix schenckii was significantly more sensitive to parsol and eusolex (MIC = 16 mu g mL(-1), for both compounds) than fluconazole (MIC = 64 mu g mL(-1)).107661665Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FUNARBEFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundacao AraucariaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Synthesis and Anti-Paracoccidioides Activity of Calix[n]arenes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fungi are some of the most neglected pathogens in terms of new drug discovery. Paracoccidioidomycosis, an endemic disease to South America, is caused by dimorphic fungi of Paracoccidioides genus. Reasonable citotoxicity, limited efficacy, and frequent use of current commercial antifungals have led to the emergence of resistance. Thus, the development of new antifungals with more selectivity and large spectrum of action is mandatory. In this work, six calix[n]arenes were synthesized and their activity explored against seven isolates of P. brasiliensis and P. lutzii. p-tert-Butylcalix[4] arene (CX1) was the most potent compound against fungal cells and exhibited the lowest toxicity on healthy mammalian cells (V79, hamster lung and MDCK, dog kidney). This is the first report on the effect of calix[n] arenes as growth inhibitors of Paracoccidioides fungi.913036Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq