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Review
. 2023 Jul 24:56:e01212023.
doi: 10.1590/0037-8682-0121-2023. eCollection 2023.

Searching for new antifungals for the treatment of cryptococcosis

Naira Sulany Oliveira de Sousa  1 , Juan Diego Ribeiro de Almeida  2 , Hagen Frickmann  3   4 , Marcus Vinícius Guimarães Lacerda  5   6   7 , João Vicente Braga de Souza  1   2
Affiliations
Review

Searching for new antifungals for the treatment of cryptococcosis

Naira Sulany Oliveira de Sousa et al. Rev Soc Bras Med Trop. .

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.

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Conflict of interest statement

Conflict of Interest: The authors declare that they have no conflicts of interest.

Figures

FIGURE 1:
FIGURE 1:. Micromorphological characteristic of Cryptococcus spp. Direct exam, prepared with Indian ink (400×).
FIGURE 2:
FIGURE 2:. Bioprospecting steps for anticryptococcal drugs, their areas of knowledge, and the clinical trials phase. Created with BioRender.com.
See this image and copyright information in PMC

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