TY - JOUR
T1 - In vivo and in vitro activity of a bis-arylidenecyclo-alkanone against fluconazole-susceptible and -resistant isolates of Candida albicans
AU - de Sá, Nívea Pereira
AU - de Paula, Lídia Fátima José
AU - Lopes, Larissa Ferreira Finamore
AU - Cruz, Lana Ivone Barreto
AU - Matos, Thelma Tirone Silvério
AU - Lino, Cleudiomar Inácio
AU - de Oliveira, Renata Barbosa
AU - de Souza-Fagundes, Elaine Maria
AU - Fuchs, Beth Burgwyn
AU - Mylonakis, Eleftherios
AU - Johann, Susana
N1 - Funding Information:
Funding was provided by a grant to BBF and EM from the Brown/Brazil Initiative and by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) , Fundação de Amparo Pesquisa Estado de Minas Gerais (FAPEMIG) , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Pró-Reitoria de Pesquisa da UFMG .
Publisher Copyright:
© 2018
PY - 2018/9
Y1 - 2018/9
N2 - Objectives: Candida albicans is a commensal organism and opportunistic pathogen associated both with superficial (mucosal and cutaneous) and systemic infections. Extensive use of antifungal agents has led to reduced susceptibility to the few existing drugs, which has encouraged the search for novel antifungal agents. Therefore, the present study investigated the antifungal activity of 2,6-bis[(E)-(4-pyridyl)methylidene]cyclohexanone (PMC) against C. albicans. Methods: The in vitro activity of PMC was evaluated against C. albicans. Additionally, an invertebrate infection model in Caenorhabditis elegans as well as two infected murine models of oral and systemic candidiasis were used to determine the antifungal efficacy of PMC in vivo. Results: Minimum inhibitory concentrations (MICs) of PMC ranged from 4–32 μg/mL against nine clinical and two reference C. albicans isolates. Interestingly, PMC inhibited filamentation in vitro at subinhibitory concentrations similar to fluconazole. PMC also showed low toxicity against murine macrophages and human erythrocytes. In the invertebrate infection model, PMC was efficient in prolonging survival of C. elegans infected with C. albicans SC5314. Treatment with PMC was efficient both in murine models of systemic and oral candidiasis and was similar to that observed with conventional drug treatments (nystatin and fluconazole). Conclusions: The results of this study indicate the therapeutic potential of PMC as it was able to inhibit filamentation of C. albicans in vitro. These alterations to the fungi by PMC resulted in a reduction of oral and systemic infection in mice. In conclusion, we present promising evidence of the anticandidal activity of PMC in vitro and in vivo.
AB - Objectives: Candida albicans is a commensal organism and opportunistic pathogen associated both with superficial (mucosal and cutaneous) and systemic infections. Extensive use of antifungal agents has led to reduced susceptibility to the few existing drugs, which has encouraged the search for novel antifungal agents. Therefore, the present study investigated the antifungal activity of 2,6-bis[(E)-(4-pyridyl)methylidene]cyclohexanone (PMC) against C. albicans. Methods: The in vitro activity of PMC was evaluated against C. albicans. Additionally, an invertebrate infection model in Caenorhabditis elegans as well as two infected murine models of oral and systemic candidiasis were used to determine the antifungal efficacy of PMC in vivo. Results: Minimum inhibitory concentrations (MICs) of PMC ranged from 4–32 μg/mL against nine clinical and two reference C. albicans isolates. Interestingly, PMC inhibited filamentation in vitro at subinhibitory concentrations similar to fluconazole. PMC also showed low toxicity against murine macrophages and human erythrocytes. In the invertebrate infection model, PMC was efficient in prolonging survival of C. elegans infected with C. albicans SC5314. Treatment with PMC was efficient both in murine models of systemic and oral candidiasis and was similar to that observed with conventional drug treatments (nystatin and fluconazole). Conclusions: The results of this study indicate the therapeutic potential of PMC as it was able to inhibit filamentation of C. albicans in vitro. These alterations to the fungi by PMC resulted in a reduction of oral and systemic infection in mice. In conclusion, we present promising evidence of the anticandidal activity of PMC in vitro and in vivo.
KW - Antifungal
KW - Bis-arylidenecyclo-alkanone
KW - Candida albicans
KW - Murine model
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U2 - 10.1016/j.jgar.2018.04.012
DO - 10.1016/j.jgar.2018.04.012
M3 - Article
C2 - 29715565
AN - SCOPUS:85052076472
VL - 14
SP - 287
EP - 293
JO - Journal of Global Antimicrobial Resistance
JF - Journal of Global Antimicrobial Resistance
SN - 2213-7165
ER -