Searching for new antifungals for the treatment of cryptococcosis
ABSTRACT There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosin...
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ftdoajarticles:oai:doaj.org/article:1f578f9337b049769387672f29973d79 2023-08-20T04:04:45+02:00 Searching for new antifungals for the treatment of cryptococcosis Naira Sulany Oliveira de Sousa Juan Diego Ribeiro de Almeida Hagen Frickmann Marcus Vinícius Guimarães Lacerda João Vicente Braga de Souza 2023-07-01T00:00:00Z https://doi.org/10.1590/0037-8682-0121-2023 https://doaj.org/article/1f578f9337b049769387672f29973d79 EN eng Sociedade Brasileira de Medicina Tropical (SBMT) http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822023000100202&lng=en&tlng=en http://www.scielo.br/pdf/rsbmt/v56/1678-9849-rsbmt-56-e0121-2023.pdf https://doaj.org/toc/1678-9849 1678-9849 doi:10.1590/0037-8682-0121-2023 https://doaj.org/article/1f578f9337b049769387672f29973d79 Revista da Sociedade Brasileira de Medicina Tropical, Vol 56 (2023) Cryptococcosis Therapeutic failures Anticryptococcal drug development Arctic medicine. Tropical medicine RC955-962 article 2023 ftdoajarticles https://doi.org/10.1590/0037-8682-0121-2023 2023-07-30T00:39:08Z ABSTRACT There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and “bypass” the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Revista da Sociedade Brasileira de Medicina Tropical 56 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Cryptococcosis Therapeutic failures Anticryptococcal drug development Arctic medicine. Tropical medicine RC955-962 |
spellingShingle |
Cryptococcosis Therapeutic failures Anticryptococcal drug development Arctic medicine. Tropical medicine RC955-962 Naira Sulany Oliveira de Sousa Juan Diego Ribeiro de Almeida Hagen Frickmann Marcus Vinícius Guimarães Lacerda João Vicente Braga de Souza Searching for new antifungals for the treatment of cryptococcosis |
topic_facet |
Cryptococcosis Therapeutic failures Anticryptococcal drug development Arctic medicine. Tropical medicine RC955-962 |
description |
ABSTRACT There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and “bypass” the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies. |
format |
Article in Journal/Newspaper |
author |
Naira Sulany Oliveira de Sousa Juan Diego Ribeiro de Almeida Hagen Frickmann Marcus Vinícius Guimarães Lacerda João Vicente Braga de Souza |
author_facet |
Naira Sulany Oliveira de Sousa Juan Diego Ribeiro de Almeida Hagen Frickmann Marcus Vinícius Guimarães Lacerda João Vicente Braga de Souza |
author_sort |
Naira Sulany Oliveira de Sousa |
title |
Searching for new antifungals for the treatment of cryptococcosis |
title_short |
Searching for new antifungals for the treatment of cryptococcosis |
title_full |
Searching for new antifungals for the treatment of cryptococcosis |
title_fullStr |
Searching for new antifungals for the treatment of cryptococcosis |
title_full_unstemmed |
Searching for new antifungals for the treatment of cryptococcosis |
title_sort |
searching for new antifungals for the treatment of cryptococcosis |
publisher |
Sociedade Brasileira de Medicina Tropical (SBMT) |
publishDate |
2023 |
url |
https://doi.org/10.1590/0037-8682-0121-2023 https://doaj.org/article/1f578f9337b049769387672f29973d79 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Revista da Sociedade Brasileira de Medicina Tropical, Vol 56 (2023) |
op_relation |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822023000100202&lng=en&tlng=en http://www.scielo.br/pdf/rsbmt/v56/1678-9849-rsbmt-56-e0121-2023.pdf https://doaj.org/toc/1678-9849 1678-9849 doi:10.1590/0037-8682-0121-2023 https://doaj.org/article/1f578f9337b049769387672f29973d79 |
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https://doi.org/10.1590/0037-8682-0121-2023 |
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Revista da Sociedade Brasileira de Medicina Tropical |
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