Amphotericin B (AmB) is a broad spectrum of antifungal drug used to treat antifungal diseases. However, due to the high toxicity of AmB, treated patients may suffer the risk of side effects, such as renal failure. Nanoencapsulation strategies have been reported to elicit low toxicity, albeit most of them possess low encapsulation efficiency. The aim of this research is to develop micellar delivery systems for AmB with reduced toxicity while maintaining its affectivity by employing retinol (RET)-conjugated amphiphilic block copolymers (ABCs) as precursors. Copolymers composed of poly(ε-caprolactone) (A) and polyethylenglycol (B) of types AB and ABA were synthesized by ring opening polymerization and subsequently conjugated with RET by Steglich esterification. ¹H-NMR spectroscopy was used to corroborate the structure of copolymers and their conjugates and determine their molecular weights. Analysis by gel permeation chromatography also found that the materials have narrow distributions. The resulting copolymers were used as precursors for delivery systems of AmB, thus reducing its aggregation and consequently causing a low haemolytic effect. Upon conjugation with RET, the encapsulation capacity was enhanced from approximately 2 wt % for AB and ABA copolymers to 10 wt %. AmB encapsulated in polymer micelles presented improved antifungal efficiency against Candida albicans and Candida auris strains compared with Fungizone^®, as deduced from the low minimum inhibitory concentration.

Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Resistance to conventional antifungal drugs and the toxicity associated with high doses highlight the need for effective antifungal therapies. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed. Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. The doubling time was also drastically affected, going from 2.8 h to 22.5 h, which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cytotoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the potential mechanisms of A. occidentale against C. albicans on a cellular level, and might provide a promising option for the design of a new treatment for invasive candidiasis.

Brazil is home to one of the greatest biodiversities on the planet, with numerous plant species with unexplored pharmacological potential. In this study, the antifungal activity and cytotoxicity of crude extracts obtained from the seeds of Sterculia foetida L., Bulbostylis capillaris (L.) Kunth ex CB Clarke, and Pouteria caimito (Ruiz & Pav.) Radlk were investigated. The previously dehydrated seeds were subjected to extraction with physiological saline (saline extract), hexane (hexane extract) and sequential extraction with hexane followed by saline (hexane-saline extract). To determine antifungal activity via disk diffusion assays, broth microdilution based on the CLSI and evaluation of cellular specificity (EC₅₀) by redox metabolism with resazurin were performed on C. albicans ATCC 14053, C. albicans ATCC 24433 and non-albicans species Candida krusei ATCC 6258 and C. glabrata ATCC 22019. Cytotoxicity was evaluated in mouse bone marrow cells by determining the cytotoxic concentration (CC₅₀/24 h). The selectivity index (SI) was calculated as the ratio between CC₅₀ and EC₅₀. Statistical analysis of the data was performed via ANOVA, with the significance level set at p < 0.05. Saline, hexane, and hexane—saline extracts of S. foetida, as well as the saline extract of B. capillaris, showed selectivity indices higher than those of ketoconazole against C. albicans and C. krusei. With respect to C. glabrata, only the saline extract of B. capillaris demonstrated greater selectivity than the reference drug. All P. caimito extracts presented lower EC₅₀/24 h values than did ketoconazole but presented a low selectivity index, suggesting high cellular toxicity. The results obtained demonstrate that the crude extracts of S. foetida and B. capillaris seeds have significant antifungal activity and represent promising sources of bioactive compounds. Future studies should focus on the purification, isolation, and characterization of the active principles responsible for the observed activity.

Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Anti-fungal drug resistance and cytotoxicity highlight the need for effective antifungal therapeutics. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed, Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. the doubling time was also drastically affected, going from 2.8 hours to 22.5 hours. Which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cy-totoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the po-tential mechanisms of A. occidentale against C. albicans on a cellular level and might provide a promising op-tion for the design of a new treatment for invasive candidiasis

Background: Candidemia and invasive Candidiasis is the most frequent clinical manifestation in immunosuppressed individuals and represents one of the most significant healthcare‐associated infections, with mortality rates ranging from 40% to 60%. Candida albicans remains the most frequently isolated species. However, non‐ albicans species such as C. parapsilosis , C. tropicalis , and C. glabrata have increased in incidence and together represent more than 90% of invasive candidiasis cases. The emergence of resistance to conventional agents such as fluconazole and the limited availability of more potent drugs such as echinocandins and liposomal amphotericin B highlight the need for alternative therapeutic options. Recent studies have reported antiviral and antimicrobial activities of naphthoquinone with aryl‐sulfonamide and sulfonate ester derivatives moieties; however, their action against fungi has rarely been explored. Objectives: To evaluate the antifungal potential of novel naphthoquinone sulfonamide and sulfonate ester derivatives against Candida spp. and to assess their applicability in experimental treatment. Methods: Fifteen derivatives were tested. Minimum inhibitory concentration was determined, cytotoxicity assays were performed on mouse peritoneal macrophages, and intracellular reactive oxygen species generation was quantified via confocal microscopy via DCF‐DA. Results: The PS04 derivative exhibited antifungal activity against C. albicans , C. tropicalis , and C. glabrata at a concentration of 250 µg/mL, while PS01 inhibited C. glabrata at 125 µg/mL. After 24 h of exposure, none of the derivatives caused significant cytotoxicity compared with untreated cells. Conclusions: PS04 demonstrated promising preliminary antifungal activity against the tested species; however, its mechanism of action remains to be elucidated.

Anacardium genus (Anacardiaceae) consists of approximately 20 species, and Anacardium microcarpum, Anacardium humile, and Anacardium occidentale are the most widely studied, because of their medicinal and nutraceutical properties. Their common name is cashew, marañon, or cajú. The leaves and flowers of A. occidentale have been used in traditional medicine to treat skin lesions and diarrhea and as anti-inflammatory agents. Previous results in our research group have shown that the leaf extract of A. occidentale possesses an interesting antifungal activity, inhibiting the proliferation and growth of Candida albicans. To identify a potential active marker for this extract, the purification of one of its major compounds by Centrifugal Partition Chromatography (CPC) was carried out in this work. First, the EtOAc fraction was separated using the CHCl3:MeOH:H2O (4:3.5:2) solvent system. We obtained 243 mg of the EtOAc fraction then it was solubilized in 5 mL of both phases. In a single CPC run, 12.5 mg of the major compound could be isolated from the extract, with a purity of over 90%, which was subsequently identified by LC-PDA-MS/MS as being the biflavone Agathisflavone showed a minimum inhibition concentration (MIC) of 250 μg/mL against C. albicans SC5314 and It did not show cytotoxicity activity in vitro. The CPC analysis described in this work allowed obtaining, in a single run, the major flavonoid of the A. occidentale leaf extract, which is now being evaluated for its antifungal potential against Candida albicans.