TY - JOUR
T1 - Anti-Candida albicans activity of thiazolylhydrazone derivatives in invertebrate and murine models
AU - Cruz, Lana Ivone Barreto
AU - Lopes, Larissa Ferreira Finamore
AU - Ribeiro, Felipe de Camargo
AU - de Sá, Nívea Pereira
AU - Lino, Cleudiomar Inácio
AU - Tharmalingam, Nagendran
AU - de Oliveira, Renata Barbosa
AU - Rosa, Carlos Augusto
AU - Mylonakis, Eleftherios
AU - Fuchs, Beth Burgwyn
AU - Johann, Susana
N1 - Funding Information:
Figure 7. Murine model treatment of systemic candidiasis. The number of colony-forming units (CFU) recovered from the C. albicans CAN14-infected C57BL/6 female mice was lower in animals treated with fluconazole (10 mg/kg) and thiazolylhydrazone derivative 2 (10 mg/kg) than in the control group that received no treatment (Newman-Keuls Multiple Comparison test). 4. Conclusions 4. Conclusions The four thiazolylhydrazone compounds presented antifungal activity against C. albicans, andTshheo fwouedr tahcitaivziotylyilnhyvditrraozaognaei ncsotmsepvoeurnaldfsu pnrgeaslepnattehdoganentisf,uhnogwalevacetrivcoitmy paoguainndsst 1Ca. naldbi2capnrse,s aenndte d shtohwe ebde satcrtievsiutylt si,nwviitthrol oawgaeirnstto xseicvietyrailn futhnegacle lplamthoodgeelnsss, thuodwieedvearn cdowmeproeutnhdes o1naens dth2atpprersoelonntegde d thteh beessut rrveisvualtlso, fwCit.ha llboiwcaenrs tionxfieccittyed inGt.hme eclelollnmelload. eTlhs estaucdtiivedit yanodf cwoemrep othuen odn2esw thasatcponrofilromngeeddi nthteh e sumrvuirvianle omf Cod. aellbbicyanresdinufceinctgedth Ge.f umnegllaolnleollaad. Tinhet haecttiovnitgyu oefacnodmkpidonuenyds 2ofwfausn cgoanl finirfmecetdedina nthime malsu.rTinheus, mdoedmelobnyst rraetdinugcitnhge tphoet efnutniaglaolflothaidsginro tuhpe otfotnhgiauzeoalhnydd rkaizdonneeyscoomf pfuonugnadls .infected animals. Thus, demonstrating the potential of this group of thiazolhydrazone compounds. Author Contributions: Conceptualization, S.J.; B.B.F. and E.M.; methodology, L.F.F.L.; F.d.C.R.; N.P.d.S. and C.I.L.; N.T.; resources, B.B.F.; E.M. and C.A.R.; writing, review and editing, S.J.; R.B.d.O.; F.d.C.R. and B.B.F.; supervision Author Contributions: Conceptualization, S.J.; B.B.F. and E.M.; methodology, L.F.F.L.; F.C.R.; N.P.d.S. and C.I.L.; N.T.; resources, B.B.F.; E.M. and C.A.R.; writing, review and editing, S.J.; R.B.d.O.; F.C.R. and B.B.F.; Funding: Funding was provided by a grant to B.B.F. and E.M. from the Brown/Brazil Initiative; Fundação de supervision S.J. and B.B.F.; funding acquisition, S.J.; B.B.F. and E.M. Amparo Pesquisa Estado de Minas Gerais (FAPEMIG) and by Conselho Nacional de Desenvolvimento Científico Funding: Funding was provided by a grant to B. B. F. and E. M. from the Brown/Brazil Initiative; Fundação de Amparo Pesquisa Estado de Minas Gerais (FAPEMIG) and by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/12
Y1 - 2018/12
N2 - Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone compounds against C. albicans. Thiazolylhydrazone compounds 1, 2, 3, and 4 were found to exert antifungal activity, with MICs of 0.125–16.0 µg/mL against C. albicans. The toxicity of the compounds was evaluated using human erythrocytes and yielded LC50 > 64 µg/mL. The compounds were further evaluated using the greater wax moth Galleria mellonella as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound 2 was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 2 reduced the fungal load on the mouse tongue; and in the systemic model it reduced the fungal burden found in the kidney when tested at 10 mg/kg. These results show that thiazolylhydrazones are an antifungal towards C. albicans with in vivo efficacy.
AB - Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone compounds against C. albicans. Thiazolylhydrazone compounds 1, 2, 3, and 4 were found to exert antifungal activity, with MICs of 0.125–16.0 µg/mL against C. albicans. The toxicity of the compounds was evaluated using human erythrocytes and yielded LC50 > 64 µg/mL. The compounds were further evaluated using the greater wax moth Galleria mellonella as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound 2 was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 2 reduced the fungal load on the mouse tongue; and in the systemic model it reduced the fungal burden found in the kidney when tested at 10 mg/kg. These results show that thiazolylhydrazones are an antifungal towards C. albicans with in vivo efficacy.
KW - Antifungal
KW - Candida albicans
KW - Thiazolylhydrazone derivatives
UR - http://www.scopus.com/inward/record.url?scp=85061665603&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061665603&partnerID=8YFLogxK
U2 - 10.3390/jof4040134
DO - 10.3390/jof4040134
M3 - Article
AN - SCOPUS:85061665603
SN - 2309-608X
VL - 4
JO - Journal of Fungi
JF - Journal of Fungi
IS - 4
M1 - 134
ER -