Maria Flaviana Bezerra Morais-Braga

Objetivo: O presente trabalho teve por finalidade avaliar a atividade antifúngica intrínseca do óleo essencial das folhas de Eupatorium intermedium DC, de sua combinação com o fluconazol contra cepas de Candida albicans e C. tropicalis e o seu efeito na transição morfológica das espécies. Método: O óleo essencial foi obtido pelo método de hidrodestilação. Foram realizados ensaios de microdiluição em placas de 96 poços para determinar a concentração Inibitória de 50% dos fungos (CI50) e uma curva de viabilidade celular foi obtida. A Concentração Fungicida Mínima (CFM) foi obtida através da subcultura em Sabourad Dextrose Agar, sendo o efeito da combinação óleo/fluconazol verificado por com concentração subinibitória do óleo. Foram utilizadas câmaras úmidas, sobre uma lâmina de microscopia para verificar o potencial do óleo essencial em inibir a transição morfológica dos fungos. Resultados: O óleo de E. intermedium de forma isolada apresenta efeito fungistático nas maiores concentrações contra as cepas fúngicas testadas. A combinação entre o óleo e o fluconazol promoveu a potencialização de efeito do fármaco. O óleo inibiu, na maior concentração avaliada, a transição morfológica de Candida albicans. Considerações finais: O óleo de E. intermedium pode ser explorado na potencialização da atividade do Fluconazol contra Candida spp, bem como na interferência da capacidade de transição morfológica desses fungos, o que é relevante na patogênese das infecções causadas por Candida spp.

Cancer is one of the leading causes of death worldwide, and although chemotherapy is widely used, drug resistance and adverse effects limit its effectiveness, making the search for new, safer, more selective, and accessible therapies urgent. Therefore, natural products stand out for their chemical characteristics, such as species of the Anacardiaceae family, especially Spondias purpurea, which is rich in phenolic compounds. Therefore, this study evaluated the in vitro cytotoxicity of ethanolic (EESP) and aqueous (AESP) extracts of the leaves of this species using MCF-7 breast cancer cells, J774 macrophages, and NCTC929 fibroblasts. To this end, S. purpurea leaves were processed and subjected to ethanolic and aqueous extraction. The extracts were evaluated for cytotoxicity and antitumor activity in vitro in MCF-7 breast cancer cells, J774 macrophages, and NCTC929 fibroblasts using resazurin-based assays. The results indicated that both extracts exerted significant cytotoxic activity against MCF-7, with the aqueous extract having a greater effect (73.4% cytotoxicity at maximum concentration). In J774 macrophages, cytotoxicity was also significant, especially for EESP, while normal fibroblasts were little affected at low concentrations, demonstrating selectivity. These effects can be attributed to the presence of phenolic compounds, known to induce apoptosis in tumor cells. These data suggest that the species represents a promising source of bioactive compounds for the development of new anticancer agents.

The morphological transition of Candida spp. is a key virulence factor that enables these fungi to cause infections in humans. This ability to shift between yeast‐like, hyphal, and pseudohyphal forms allows Candida species to adapt to diverse environments and hostile conditions, playing a critical role in pathogenicity. In this study, we investigated the effects of synthetic chalcones on the morphological transition of Candida albicans and Candida tropicalis , alongside an in silico evaluation of the compounds’ pharmacokinetic properties, including absorption, distribution, metabolism, excretion, and toxicity (ADMET). To assess the inhibitory effects of chalcones and fluconazole on morphological transition, humid chambers were prepared and analyzed through optical microscopy. The predictions were performed using MarvinSketch (ChemAxon method), pkCSM, SMARTCyp, and Pred‐Skin 3.0 platforms. The chalcones (1E,4E)‐1,5‐diphenylpenta‐1,4‐dien‐3‐one (DB‐Acetone), (1E,3E,6E,8E)‐1,9‐diphenylnona‐1,3,6,8‐tetraen‐5‐one (DB‐CNM), and (1E,4E)‐1,5‐bis (4‐methoxyphenyl)penta‐1,4‐dien‐3‐one (DB‐Anisal), as well as fluconazole, completely inhibited fungal morphological transition at the tested concentrations (MC, 1024 μ g/mL, and MC/2, 512 μ g/mL). In silico analyses revealed high intestinal absorption for all chalcones, with DB‐Acetone and DB‐Anisal showing potential for significant oral bioavailability. Moreover, all compounds demonstrated extensive tissue distribution and the ability to cross the blood‐brain barrier. Despite some limitations, DB‐Acetone, DB‐CNM, and DB‐Anisal were predicted to be well tolerated at high doses, with DB‐Anisal emerging as the safest candidate based on toxicity profiles. Overall, these findings suggest that the synthetic chalcones studied are promising agents for inhibiting the morphological transition of C. albicans and C. tropicalis , with DB‐Anisal showing the most favorable pharmacokinetic and safety profile.

The incidence of opportunistic fungal infections caused by species of the genus Candida is characterized as a serious threat to global health. Natural products are therefore emerging as possible therapeutic agents to be used in the treatment of these infections. The aim of this study was to investigate the antifungal potential of the essential oil from the leaves of Nectandra grandiflora Nees & Mart against opportunistic strains of the Candida genus. For the tests, the standard strains Candida albicans INCQS 40006 and Candida tropicalis INCQS 40042 were used. The 50 % inhibitory concentration (Cl50) and the intrinsic and combined activity of the oil with fluconazole were evaluated using the broth microdilution method; the Minimum Fungicidal Concentration (MFC) and the effect on the morphological transition of the fungi were evaluated by subcultivation in Petri dishes and in a humid chamber, respectively. In the Cl50 test, the oil was found to be more active against C. albicans. The combination of essential oil and fluconazole obtained the best Cl50 value for both C. albicans and C. tropicalis. The growth inhibition curve showed a concentration-dependent effect. The CFM test showed only a fungistatic effect for both strains. The essential oil of N. grandiflora had an inhibitory effect and reduced the morphological transition of C. albicans; however, it had no effect on the morphological transition of C. tropicalis. Thus, it was found that the essential oil of N. grandiflora was able to potentiate the effect of the drug fluconazole on C. albicans and C. tropicalis, and to inhibit the pleomorphism of C. albicans. A incidência de infecções fúngicas oportunistas causadas por espécies do gênero Candida, caracteriza-se como grave ameaça à saúde pública global. Assim, produtos naturais surgem como possíveis agentes terapêuticos a serem utilizados no tratamento dessas infecções. No presente trabalho, buscou-se investigar o potencial antifúngico do óleo essencial das folhas de Nectandra grandiflora contra cepas oportunistas do gênero Candida. Para os ensaios foram utilizadas as cepas padrão de Candida albicans INCQS 40006 e de Candida tropicalis INCQS 40042. A concentração inibitória de 50 % e a atividade intrínseca e combinada do óleo com o fluconazol foram avaliadas através do método de microdiluição em caldo; já a Concentração Fungicida Mínima e o efeito na transição morfológica dos fungos foram avaliadas por subcultivo em placa de Petri e em câmara úmida, respectivamente. No ensaio de concentração inibitória de 50 %, foi constatada melhor atividade do óleo contra C. albicans. A combinação óleo essencial com o fluconazol obteve melhor valor na concentração inibitória de 50 % tanto para C. albicans como para C. tropicalis. A curva de inibição de crescimento demonstrou efeito dependente do aumento da concentração. No ensaio da Concentração Fungicida Mínima verificou-se apenas efeito fungistático, para ambas as cepas. O óleo essencial de N. grandiflora apresentou efeito de inibição e redução na transição morfológica de C. albicans, no entanto, não apresentou efeito na transição morfológica de C. tropicalis. Dessa forma, constatou-se que o óleo essencial de N. grandiflora foi capaz de potencializar o efeito do fármaco fluconazol sobre C. albicans e C. tropicalis, e de inibir o pleomorfismo de C. albicans.

Biofilms, formed by microbial communities that increase resistance to antibiotics, are responsible for chronic infections, making their combat a therapeutic priority. Taking this into account, the fruit Caryocar coriaceum stands out for its potential in the treatment of infectious diseases. The different parts of this plant can be used, and the fixed oil extracted from its fruit, rich in fatty acids, is indicated as responsible for its biological activities. Thus, the objective of this study was to evaluate the chemical composition of the fixed oil extracted from the fruits of C. coriaceum (FOCC), in addition to analyzing its action in the inhibition and pre-formed biofilm disruption of bacteria. The fixed oil was extracted from the internal mesocarp through exhaustive extraction with n-hexane, resulting in a yield of 38.29%. For antibiofilm evaluation, multidrug-resistant bacterial strains were exposed to the oil, and the antibiofilm activity was verified through biofilm formation and pre-formed biofilm disruption assays. The chemical analysis of the fixed oil of C. coriaceum (FOCC) identified eight fatty acids, representing 98.2% of the total composition, with a predominance of oleic acid (60.1%) and palmitic acid (33.5%). FOCC demonstrated approximately 70% inhibition of Streptococcus mutans biofilm formation at a concentration of 10 mg/mL and approximately 60% inhibition against Staphylococcus aureus and Pseudomonas aeruginosa. In pre-formed biofilm disruption, FOCC showed low efficacy against S. mutans and P. aeruginosa but showed greater activity against Enterococcus faecalis and S. aureus. These results indicate that FOCC has the potential to prevent biofilms, but its pre-formed biofilm disruption capacity is still limited.

Background: Phytol is a diterpene from the long-chain unsaturated acyclic alcohols, known for its diverse biological effects, including antimicrobial and anti-inflammatory activities. Present in essential oils, phytol is a promising candidate for various applications in the pharmaceutical and biotechnological sectors. This study aimed to evaluate the in vitro antibacterial and drug-potentiating effects of phytol against multidrug-resistant bacteria and to evaluate its in silico properties: ADME and molecular docking. Methods: The in vitro antibacterial activity of phytol and the phytol combined with conventional drugs was evaluated by microdilution tests against standard and resistant bacterial strains. Finally, the SwissADME platform was employed to analyse the physicochemical and pharmacokinetic characteristics of phytol. Results: Phytol significantly reduced the Minimum Inhibitory Concentration (MIC) of norfloxacin and gentamicin required to inhibit multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, respectively. Additionally, ADME analysis revealed that phytol exhibits low toxicity and favourable pharmacokinetic properties; in addition, it is revealed through molecular docking that phytol showed a relevant affinity with the proteins 6GJ1 and 5KDR, however, with values lower than the drugs gentamicin and ampicillin. Conclusions: Collectively, these findings suggest that phytol holds potential as an effective adjuvant in combating antimicrobial resistance.

Multidrug-resistant bacteria have complicated the treatment of gastrointestinal diseases; their microbial resistance stems from the indiscriminate use of medications and the transfer of resistance genes. Varronia curassavica Jacq., a plant traditionally used to treat rheumatic and gastrointestinal diseases in underserved populations, has sparked interest as a potential source of antimicrobial compounds. This study aimed to investigate the chemical composition and antibacterial effects of V. curassavica essential oil and to evaluate its toxicity in Drosophila melanogaster. The essential oil was extracted through hydrodistillation and its chemical composition was determined using GC-MS. Antibacterial tests were performed with microdilution. The results showed the presence of major compounds including α-pinene and β-caryophyllene. The essential oil did not show relevant MIC, but it enhanced the effects of the antibiotics, gentamicin, norfloxacin, and oxacillin. It exhibited no toxicity and did not affect geotaxis, even at high concentrations. The in silico analysis of α-pinene revealed low toxicity; however, its permeability to the BBB shows that caution is needed in its application. These results indicate that the essential oil of V. curassavica shows promising potential in enhancing pharmaceuticals to prevent increased bacterial resistance. In addition, it demonstrated safe aspects when tested on D. melanogaster.

Varronia curassavica Jacq. is an aromatic species appertaining to the Boraginaceae family and has been mentioned for its numerous traditional uses and pharmacological properties, especially its antimicrobial and anti-inflammatory effects. The aim of the present study was to investigate the phytochemical profile and antifungal activities of the essential oils of V. curassavica, in addition to analyzing the ADMET properties of the majority components. The GC-MS analysis of V. curassavica essential oil (EOVC) comprised 97.36% of total composition, with α-pinene, β-caryophyllene, and bicyclogermacrene (44.46%, 22.87%, and 13.05%, respectively) as the main constituents among other minor/trace constituents. The antifungal activity of EOVC was evaluated against three Candida species and was observed with IC₅₀ > 200 μg/mL. Remarkably, the combination of EOVC with fluconazole significantly reduced the IC₅₀ required for the drug to inhibit C. tropicalis (0.003 μg/mL), C. albicans (0.7996 μg/mL), and C. krusei (17.73 μg/mL). In addition, ADME/Tox studies using α-pinene revealed that the compound poses no toxicity threats but requires caution due to its high permeability to the blood–brain barrier (BBB). Overall, the obtained results suggest that Varronia curassavica essential oil is a potentially good antifungal agent for combating fungal resistance.