Overview of Antifungal Drugs against Paracoccidioidomycosis: How Do We Start, Where Are We, and Where Are We Going?

Silva, Lívia do Carmo; Oliveira, Amanda Alves de; Souza, Dienny Rodrigues de; Barbosa, Katheryne Lohany Barros; Silva, Kleber Santiago Freitas e; Júnior, Marcos Antonio Batista de Carvalho; Rocha, Olívia Basso; Lima, Raisa Melo; Santos, Thaynara Gonzaga; Soares, Célia Maria de Almeida; Pereira, Maristela

doi:10.3390/jof6040300

Cited by 16 publications

(12 citation statements)

References 145 publications

(181 reference statements)

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“…Therefore, it is necessary to search for new therapeutic alternatives that reduce treatment time and, consequently, side effects. Such new broadened approaches were the object of recent reviews [ 14 , 15 ].…”

Section: Paracoccidioides and Paracoccidioidomymentioning

confidence: 99%

Paracoccidioidomycosis Protective Immunity

Burger

2021

JoF

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Protective immunity against Paracoccidioides consists of a stepwise activation of numerous effector mechanisms that comprise many cellular and soluble components. At the initial phase of non-specific innate immunity, resistance against Paracoccidioides comes from phagocytic polymorphonuclear neutrophils, natural killer (NK) cells and monocytes, supplemented by soluble factors such as cytokines and complement system components. Invariant receptors (Toll-like receptors (TLRs), Dectins) which are present in cells of the immune system, detect patterns present in Paracoccidioides (but not in the host) informing the hosts cells that there is an infection in progress, and that the acquired immunity must be activated. The role of components involved in the innate immunity of paracoccidioidomycosis is herein presented. Humoral immunity, represented by specific antibodies which control the fungi in the blood and body fluids, and its role in paracoccidioidomycosis (which was previously considered controversial) is also discussed. The protective mechanisms (involving various components) of cellular immunity are also discussed, covering topics such as: lysis by activated macrophages and cytotoxic T lymphocytes, the participation of lytic products, and the role of cytokines secreted by T helper lymphocytes in increasing the efficiency of Paracoccidioides, lysis.

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Section: Paracoccidioides and Paracoccidioidomymentioning

confidence: 99%

Paracoccidioidomycosis Protective Immunity

Burger

2021

JoF

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“…Sulfamethoxazole is indicated when associated with trimethoprim (an association known as cotrimoxazole). Among the advantages of this association are the low cost, good tolerance, safety for prolonged use [19], and good penetration in the central nervous system [36]. Cotrimoxazole is used in patients with mild to moderate forms of PCM and neuroparacoccidioidomycosis [36].…”

Section: Paracoccidioidomycosis: Disease Diagnosis and Treatmentmentioning

confidence: 99%

“…Among the advantages of this association are the low cost, good tolerance, safety for prolonged use [19], and good penetration in the central nervous system [36]. Cotrimoxazole is used in patients with mild to moderate forms of PCM and neuroparacoccidioidomycosis [36]. Although the side effects of itraconazole and cotrimoxazole (e.g., nausea, vomiting, and diarrhea) can make treatment difficult, overall both drugs are well tolerated by patients with PCM.…”

Section: Paracoccidioidomycosis: Disease Diagnosis and Treatmentmentioning

confidence: 99%

“…Despite the effectiveness of amphotericin B, it produces several toxic effects in the host, including acute symptoms, such as nausea, vomiting, fever, hyper-and hypotension, and hypoxia, in addition to chronic nephrotoxicity. New formulations, such as amphotericin B lipid complex, liposomal amphotericin B, and amphotericin B colloidal dispersion, have yielded better tissue distribution and less toxicity [36].…”

Section: Paracoccidioidomycosis: Disease Diagnosis and Treatmentmentioning

confidence: 99%

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Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation

Chaves

Navarro

Barros

et al. 2021

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The dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in rural areas. PCM is considered a neglected disease, despite being a disabling disease that has a notable impact on the public health system. Paracoccidioides spp. are thermally dimorphic fungi that present infective mycelia at 25 °C and differentiate into pathogenic yeast forms at 37 °C. This transition involves a series of morphological, structural, and metabolic changes which are essential for their survival inside hosts. As a pathogen, the fungus is subjected to several varieties of stress conditions, including the host immune response, which involves the production of reactive nitrogen and oxygen species, thermal stress due to temperature changes during the transition, pH alterations within phagolysosomes, and hypoxia inside granulomas. Over the years, studies focusing on understanding the establishment and development of PCM have been conducted with several limitations due to the low effectiveness of strategies for the genetic manipulation of Paracoccidioides spp. This review describes the most relevant biological features of Paracoccidioides spp., including aspects of the phylogeny, ecology, stress response, infection, and evasion mechanisms of the fungus. We also discuss the genetic aspects and difficulties of fungal manipulation, and, finally, describe the advances in molecular biology that may be employed in molecular research on this fungus in the future.

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“…Paracoccidioidomycosis is an endemic infection in Latin America, and most cases occur in Brazil, Argentina, Colombia, Ecuador, Venezuela, and Paraguay [ 28 , 29 ]. The standard treatment for both mycoses is amphotericin B and itraconazole; however, the antibacterial cotrimoxazole (sulfamethoxazole/trimethoprim combination) is also indicated for paracoccidioidomycosis [ 30 , 31 , 32 , 33 ]. Cases related to nephrotoxicity, hepatotoxicity, and drug interactions increase considerably in these diseases, as they are considered systemic and require long treatments that can last for up to 24 months [ 26 , 31 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives

et al. 2022

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Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, Histoplasma capsulatum, and Paracoccidioides brasiliensis. In this work, a series of nitrofuran derivatives were synthesized and tested against different fungal species; most of them showed inhibitory activity, fungicide, and fungistatic profile. The minimal inhibitory concentration (MIC90) values for the most potent compounds range from 0.48 µg/mL against H. capsulatum (compound 11) and P. brasiliensis (compounds 3 and 9) to 0.98 µg/mL against Trichophyton rubrum and T. mentagrophytes (compounds 8, 9, 12, 13 and 8, 12, 13, respectively), and 3.9 µg/mL against Candida and Cryptococcus neoformans strains (compounds 1 and 5, respectively). In addition, all compounds showed low toxicity when tested in vitro on lung cell lines (A549 and MRC-5) and in vivo in Caenorhabditis elegans larvae. Many of them showed high selectivity index values. Thus, these studied nitrofuran derivatives proved to be potent against different fungal species, characterized by low toxicity and high selectivity; for these reasons, they may become promising compounds for the treatment of mycoses.

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Overview of Antifungal Drugs against Paracoccidioidomycosis: How Do We Start, Where Are We, and Where Are We Going?

Cited by 16 publications

References 145 publications

Paracoccidioidomycosis Protective Immunity

Paracoccidioidomycosis Protective Immunity

Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation

Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives

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