Antifungal drugs: New insights in research &amp; development

Nicola, André Moraes; Albuquerque, Patrícia; Paes, Hugo Costa; Fernandes, Larissa; Costa, Fabrício F.; Kioshima, Érika Seki; Abadio, Ana Karina Rodrigues; Bocca, Anamélia Lorenzetti; Felipe, Maria Sueli Soares

doi:10.1016/j.pharmthera.2018.10.008

Cited by 105 publications

(73 citation statements)

References 206 publications

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“…In addition to these two antibodies that made it to clinical development, several other antibodies have been proposed as candidates for immunotherapy of fungal diseases (Nicola et al, 2018). An anti-β-glucan monoclonal antibody (mAb 2G8) was protective in animal models of invasive mycoses (Rachini et al, 2007), consistent with the protection afforded by a β-glucan vaccine (Torosantucci et al, 2005).…”

Section: Discussionmentioning

confidence: 84%

Thioredoxin Reductase 1 Is a Highly Immunogenic Cell Surface Antigen in Paracoccidioides spp., Candida albicans, and Cryptococcus neoformans

et al. 2020

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Section: Discussionmentioning

confidence: 84%

Thioredoxin Reductase 1 Is a Highly Immunogenic Cell Surface Antigen in Paracoccidioides spp., Candida albicans, and Cryptococcus neoformans

et al. 2020

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“…[ 18,33,34 ] Compounds 3 , 5a–g , 6a–g , 7a–g , 8a–g , and 9a–g were tested for antifungal properties against two clinically important fungal species, Candida albicans and Cryptococcus neoformans , which are involved in invasive fungal infections in immunocompromised patients, leading to high risk of morbidity and mortality. [ 51–53 ]…”

Section: Resultsmentioning

confidence: 99%

New thiazolyl‐pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents

Cuartas

Robledo

Vélez

et al. 2020

Archiv der Pharmazie

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A new series of N-substituted pyrazoline derivatives 6a-g, 7a-g, 8a-g, and 9a-g was synthetized by reaction of hydrazine derivatives and chalcone-thiazole hybrids bearing nitrogen mustard 5a-g. The chalcones 5a-g were obtained by Claisen-Schmidt condensation of thiazole-2-nitrogen mustard 3 and selected acetophenones 4a-g. These new compounds 6/7/8/9a-g were screened for their antifungal activity against Cryptococcus neoformans, with IC 50 values of 3.9-7.8 µg/ml for the N-3, 5-dichlorophenyl pyrazolines 9e-g. Interestingly, those compounds show low cytotoxic effects toward erythrocytes (RBC). In addition, N-acetyl (6a,b) and N-formyl pyrazolines (7a, 7b, 7c, and 7g) showed inhibitory activity against methicillinsusceptible Staphylococcus aureus, methicillin-resistant S. aureus, and vancomycinintermediate S. aureus, with the most important minimum inhibitory concentration values ranging from 31.25 to 125 µg/ml. Regarding the antiprotozoal activity, thiazolyl-pyrazolines 9g, 8f, and 7c display high activity against Plasmodium falciparum, Leishmania (V) panamensis, and Trypanosoma cruzi, with EC 50 values of 11.80, 6.46, and 4.98 μM, respectively, and with 7c being approximately 2.6-fold more potent than benznidazole with a selectivity index of 1.61 on U-937 human cells, showing promising potential as a novel antitrypanosomal agent. K E Y W O R D S antibacterial activity, antifungal activity, antiprotozoal activity, chalcone, pyrazoline

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“…Antimicrobial peptides (AMPs) have been identified in virtually all organisms and have diverse structures and functions, such as antimicrobial and immunomodulatory activities [4][5][6][7][8]. Because AMPs exhibit broad-spectrum activity against microorganisms and insusceptibility to conventional drug resistance mechanisms, AMPs are promising candidates for the development of new antifungal drugs [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

The interaction between Carbohydrates and the Antimicrobial Peptide P-113Tri is Involved in the Killing of Candida albicans

2020

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The emergence of drug resistance to Candida albicans is problematic in the clinical setting. Therefore, developing new antifungal drugs is in high demand. Our previous work indicated that the antimicrobial peptide P-113Tri exhibited higher antifungal activity against planktonic cells, biofilm cells, and clinical isolates of Candida species compared to its parental peptide P-113. In this study, we further investigated the difference between these two peptides in their mechanisms against C. albicans. Microscopic examination showed that P-113 rapidly gained access to C. albicans cells. However, most of the P-113Tri remained on the cell surface. Moreover, using a range of cell wall-defective mutants and competition assays, the results indicated that phosphomannan and N-linked mannan in the cell wall are important for peptide binding to C. albicans cells. Furthermore, the addition of exogenous phosphosugars reduced the efficacy of the peptide, suggesting that negatively charged phosphosugars also contributed to the peptide binding to the cell wall polysaccharides. Finally, using a glycan array, P-113Tri, but not P-113, can bind to other glycans commonly present on other microbial and mammalian cells. Together, these results suggest that P-113 and P-113Tri have fundamental differences in their interaction with C. albicans and candidacidal activities.

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Antifungal drugs: New insights in research & development

Cited by 105 publications

References 206 publications

Thioredoxin Reductase 1 Is a Highly Immunogenic Cell Surface Antigen in Paracoccidioides spp., Candida albicans, and Cryptococcus neoformans

Thioredoxin Reductase 1 Is a Highly Immunogenic Cell Surface Antigen in Paracoccidioides spp., Candida albicans, and Cryptococcus neoformans

New thiazolyl‐pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents

The interaction between Carbohydrates and the Antimicrobial Peptide P-113Tri is Involved in the Killing of Candida albicans

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