Rotenone enhances antifungal activity of novel pyrazoles against Candida spp.

European Journal of Medicinal Chemistry Reports

Renata de Almeida¹  Alice Maria Rolim Bernardino²  Percilene Fazolin Vegi³  Maurício Silva dos Santos⁴  Robson Xavier Faria⁵  Mauricio Afonso Vericimo⁶  Luis Fernando Quejada⁷ 

[1]Laboratory of Immunology and Infectious and Granulomatous Diseases, Department of Biology, Fluminense Federal University, Niterói, RJ, Brazil

[2]Postgraduate Program in Pathology, Fluminense Federal University, Niterói, RJ, Brazil

[3]Postgraduate Program in Science and Biotechnology, Fluminense Federal University, Niterói, RJ, Brazil

[4]Laboratory of Immunology and Infectious and Granulomatous Diseases, Department of Biology, Fluminense Federal University, Niterói, RJ, Brazil

[5]Multicentric Postgraduate Program in Chemistry (PPGMQ-MG), Institute of Physics and Chemistry, Federal University of Itajubá, Itajubá, MG, Brazil

[6]Postgraduate Program in Chemistry, Institute of Chemistry, Fluminense Federal University, Niterói, RJ, Brazil

[7]Proteomics and Human Mycosis Unit, Group of Infectious Diseases Department of Microbiology, Faculty of Sciences, Pontificia Universidad Javeriana, Carrera 7 No. 43-82, Bogotá, D.C, 110231, Colombia

关键词: Invasive mycoses;    Candida;    Pyrazoles;    Imidazolines;    Rotenone;    Antifungals;   

DOI  :  

来源: DOAJ

【 摘 要 】

Mycoses annually affect about 2 million individuals worldwide, especially in tropical countries. Candida spp., one of the main etiologic agents of these mycoses, and in particular Candida albicans has been the most isolated pathogen in patients with severe clinical cases of invasive candidiasis and candidemia, causing frequent infections or opportunistic and chronic systemic forms. However, the emergence of non-albicans infections has become a public health concern worldwide. In discovering har.mless molecules, the pyrazoles have attracted many scientists because their great synthetic versatility and extensive therapeutic properties such as antibacterials, antivirals, antimalarials, and anti-inflammatories, anti-leishmaniasis, and antifungals. They are part of Azole compounds used for decades for antifungal treatment. The azole action mechanism is related to ergosterol synthesis inhibition by blocking the target enzymes, known as Erg11p, leading to fungistatic action. We evaluated the antifungal potential of 12 pyrazole derivatives. Compound 1d caused prominent action against Candida glabrata. Thus, we employed Rotenone as a mitochondrial complex I inhibitor. Rotenone helped to enhance the effect of the novel pyrazole derivatives tested against Candida spp, decreasing MICs value from a range of 250–500 to <3.1 ​μg/mL. Pyrazoles had a reduced cytotoxicity effect on in vivo cell culture than ketoconazole. Although ROS production might be a possible mechanism, it remained unclear. Thus, new studies must elucidate this synergistic action.

【 授权许可】

Unknown