Rotenone enhances antifungal activity of novel pyrazoles against Candida spp.
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | European Journal of Medicinal Chemistry Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772417422000176 |
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| author | Luis Fernando Quejada Renata de Almeida Percilene Fazolin Vegi Maurício Silva dos Santos Alice Maria Rolim Bernardino Mauricio Afonso Vericimo Robson Xavier Faria |
| author_facet | Luis Fernando Quejada Renata de Almeida Percilene Fazolin Vegi Maurício Silva dos Santos Alice Maria Rolim Bernardino Mauricio Afonso Vericimo Robson Xavier Faria |
| author_sort | Luis Fernando Quejada |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T23:16:46Z |
| format | Article |
| id | doaj.art-d005fad141754b17ab111139b5a24439 |
| institution | Directory Open Access Journal |
| issn | 2772-4174 |
| language | English |
| last_indexed | 2024-04-13T23:16:46Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Medicinal Chemistry Reports |
| spelling | doaj.art-d005fad141754b17ab111139b5a244392022-12-22T02:25:24ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742022-08-015100045Rotenone enhances antifungal activity of novel pyrazoles against Candida spp.Luis Fernando Quejada0Renata de Almeida1Percilene Fazolin Vegi2Maurício Silva dos Santos3Alice Maria Rolim Bernardino4Mauricio Afonso Vericimo5Robson Xavier Faria6Proteomics 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; Laboratory of Immunology and Infectious and Granulomatous Diseases, Department of Biology, Fluminense Federal University, Niterói, RJ, Brazil; Postgraduate Program in Science and Biotechnology, Fluminense Federal University, Niterói, RJ, BrazilLaboratory of Immunology and Infectious and Granulomatous Diseases, Department of Biology, Fluminense Federal University, Niterói, RJ, Brazil; Postgraduate Program in Pathology, Fluminense Federal University, Niterói, RJ, BrazilPostgraduate Program in Chemistry, Institute of Chemistry, Fluminense Federal University, Niterói, RJ, BrazilMulticentric Postgraduate Program in Chemistry (PPGMQ-MG), Institute of Physics and Chemistry, Federal University of Itajubá, Itajubá, MG, BrazilPostgraduate Program in Chemistry, Institute of Chemistry, Fluminense Federal University, Niterói, RJ, BrazilLaboratory of Immunology and Infectious and Granulomatous Diseases, Department of Biology, Fluminense Federal University, Niterói, RJ, Brazil; Postgraduate Program in Science and Biotechnology, Fluminense Federal University, Niterói, RJ, Brazil; Postgraduate Program in Pathology, Fluminense Federal University, Niterói, RJ, BrazilPostgraduate Program in Science and Biotechnology, Fluminense Federal University, Niterói, RJ, Brazil; Toxoplasmosis and other Protozoa Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation-FIOCRUZ, 21045-900, Rio de Janeiro, RJ, Brazil; Corresponding author. Toxoplasmosis and other Protozoa Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation-FIOCRUZ, 21045-900, Rio de Janeiro, RJ, Brazil.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.http://www.sciencedirect.com/science/article/pii/S2772417422000176Invasive mycosesCandidaPyrazolesImidazolinesRotenoneAntifungals |
| spellingShingle | Luis Fernando Quejada Renata de Almeida Percilene Fazolin Vegi Maurício Silva dos Santos Alice Maria Rolim Bernardino Mauricio Afonso Vericimo Robson Xavier Faria Rotenone enhances antifungal activity of novel pyrazoles against Candida spp. European Journal of Medicinal Chemistry Reports Invasive mycoses Candida Pyrazoles Imidazolines Rotenone Antifungals |
| title | Rotenone enhances antifungal activity of novel pyrazoles against Candida spp. |
| title_full | Rotenone enhances antifungal activity of novel pyrazoles against Candida spp. |
| title_fullStr | Rotenone enhances antifungal activity of novel pyrazoles against Candida spp. |
| title_full_unstemmed | Rotenone enhances antifungal activity of novel pyrazoles against Candida spp. |
| title_short | Rotenone enhances antifungal activity of novel pyrazoles against Candida spp. |
| title_sort | rotenone enhances antifungal activity of novel pyrazoles against candida spp |
| topic | Invasive mycoses Candida Pyrazoles Imidazolines Rotenone Antifungals |
| url | http://www.sciencedirect.com/science/article/pii/S2772417422000176 |
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