Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising strategy to enhance efficacy and overcome resistance. This study investigated the antifungal activity of five naphthoquinones against nine isolates of Cryptococcus spp. and assessed their synergistic effects with amphotericin B (AmB). Methods: In this study, five selected naphthoquinones were evaluated for their antifungal activity against Cryptococcus spp. isolates using broth microdilution assays to determine minimum inhibitory concentrations (MICs), according to CLSI guidelines. The potential synergistic effect with AmB was assessed using checkerboard assays, with synergy interpreted based on the fractional inhibitory concentration index (FICI). Cytotoxicity was evaluated in MRC-5 human lung fibroblast cells using the MTT assay. Results: Among the compounds tested, 2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated antifungal activity, with MIC values ranging from 3.12 to 12.5 µg/mL. Checkerboard assays revealed a synergistic interaction between 2-MNQ and AmB, with a fractional inhibitory concentration index (FICI) of 0.27. The combination reduced the MIC of AmB by 4.17-fold. These findings highlight the potential of synthetic naphthoquinones, particularly 2-MNQ, as effective antifungal agents with synergistic properties when combined with AmB. The observed synergy suggests complementary mechanisms, including increased fungal membrane permeability and oxidative stress induction. Conclusions: This study highlights the potential of 2-MNQ and 2,3-DBNQ as antifungal candidates against Cryptococcus spp., with emphasis on the synergistic interaction observed between 2-MNQ and amphotericin B. The findings reinforce the importance of structural modifications in naphthoquinones to enhance antifungal activity and support the need for further preclinical studies investigating combination therapies aimed at improving treatment efficacy in patients with cryptococcosis.

Macrofungal diversity is essential to forest ecosystems, supporting carbon cycling and plant community structure. However, anthropogenic disturbance threatens this diversity, particularly near urban areas. In Manaus, irregular settlements affect forest fragments such as the Adolpho Ducke Forest Reserve. This study described patterns of macrofungal diversity in preserved and anthropized sectors of an Amazonian forest. The study was conducted during a single field campaign in July 2024 and compared two sectors of the Adolpho Ducke Forest Reserve: one preserved forest sector and one anthropized sector. In each sector, 600 m2 were surveyed across six 10 × 10 m plots. Sampling was performed through active searches along predefined transects, using standardized field effort per plot and the same field observer/team in both sectors. Fungal diversity was analyzed using species accumulation data, morphological and molecular identification, including phylogenetic tree construction and quantification of basidiomata per taxon, and ecological indices (Shannon-Wiener diversity index, Pielou’s evenness, and Sørensen similarity index). A total of 91 basidiomata and 31 taxa were recorded in the preserved sector, with Marasmius spp., Mycena spp., Amauroderma spp., Auricularia spp., and Schizophyllum spp. as the most frequent taxa. In the anthropized sector, 15 basidiomata and 8 taxa were recorded, with Trametes sp., Marasmius puttemasii, Schizophyllum sp., Pycnoporus sp., and an unidentified Agaricales morphotype as the most frequent taxa. Ecological index analysis indicated higher diversity in the preserved sector (H′ = 3.24) and slightly lower Pielou’s evenness (J) = 0.94, whereas the anthropized sector showed lower diversity (H′ = 1.97) and slightly higher Pielou’s evenness (J) = 0.95. These results suggest that anthropogenic influence may be associated with reduced macrofungal diversity at the forest-city interface.