Objective: This study evaluated the antifungal activity of cinnamaldehyde on Candida spp. In vitro and in situ assays were carried out to test cinnamaldehyde for its anti-Candida effects, antibiofilm activity, effects on fungal micromorphology, antioxidant activity, and toxicity on keratinocytes and human erythrocytes. Statistical analysis was performed considering α = 5%. Results: The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of cinnamaldehyde ranged from 18.91 μM to 37.83 μM. MIC values did not change in the presence of 0.8 M sorbitol, whereas an 8-fold increase was observed in the presence of ergosterol, suggesting that cinnamaldehyde may act on the cell membrane, which was subsequently confirmed by docking analysis. The action of cinnamaldehyde likely includes binding to enzymes involved in the formation of the cytoplasmic membrane in yeast cells. Cinnamaldehyde-treated microcultures showed impaired cellular development, with an expression of rare pseudo-hyphae and absence of chlamydoconidia. Cinnamaldehyde reduced biofilm adherence by 64.52% to 33.75% (p < 0.0001) at low concentrations (378.3–151.3 µM). Cinnamaldehyde did not show antioxidant properties. Conclusions: Cinnamaldehyde showed fungicidal activity through a mechanism of action likely related to ergosterol complexation; it was non-cytotoxic to keratinocytes and human erythrocytes and showed no antioxidant activity.
Fungal infections, including those caused by Candida spp., are recognized in immunocompromised individuals for their high rates of morbidity and mortality. Microorganism resistance to conventional drugs compromises treatment effectiveness and yet also reveals the need to develop new drugs. In many compounds, nitro groups contribute to antimicrobial activity; thus, the inhibitory activity of a collection of twenty esters and amides (derived from 3,5-dinitrobenzoic acid) against Candida spp. was elucidated using microdilution methods to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicide Concentration (MFC), as well as probable mechanisms of action. The structures of the synthesized compounds were characterized by FTIR spectroscopy, 1H-NMR, 13C NMR, and HRMS. Of the tested derivatives, ten presented fungicidal activity against at least one of the tested strains. Ethyl 3,5-dinitrobenzoate (2) exhibited the most potent antifungal activity against Candida albicans (MIC=125µg/mL; 0.52mM), Candida krusei (MIC=100µg/mL; 4.16mM), and Candida tropicalis (MIC=500µg/ml; 2.08mM). The structure of the second most potent derivative (propyl 3,5-dinitrobenzoate (3) reveals that esters with short alkyl side chains exhibit better biological activity profiles. Compounds 2 and 3 presented a mechanism of action involving the fungal cell membrane. Though compound 2 modeling against C. albicans revealed a multitarget antifungal mechanism of action, involving various cellular processes, interference in the synthesis of ergosterol was observed. Our results demonstrate that certain ester derivatives containing aromatic ring nitro groups may be useful in the search for new antifungal drugs.
The plant species C. sativum L. is a staple in cuisine and holds significant ethnopharmacological value. Its essential oil (EO) is of particular interest, yet its toxicity profile remains a subject of inquiry. This study aimed to elucidate the chemical constituents of C. sativum L. EO and evaluate its toxicity through various parameters, including cytotoxicity assays on HaCaT keratinocytes, in vivo toxicity tests on Galleria mellonella larvae, in vivo genotoxicity assessments on mice and cytotoxicity assays on human erythrocytes. Notably, major constituents such as 2-decen-1-ol, dec-(2E)-enal, and 1,6-octadien-3-ol were found to remain predominant. The IC50 value for the essential oil on the keratinocyte cell line was determined to be 60.13 ± 2.02 µg/mL. However, in vivo toxicity tests with G. mellonella larvae demonstrated safety at doses below 4.5 g/kg. Additionally, genotoxicity assessment revealed that a single dose of 20 mg/mL (5 mg/kg) did not induce a significant increase in micronuclei formation. EO concentrations above 250 µg/mL led to significant changes in human erythrocytes cell viability (p < 0.0001), resulting in over 60% hemolysis. These findings collectively suggest that the essential oil of C. sativum L. exhibits a suitable toxicity profile for conducting preclinical studies in vertebrate animal models.
Products derived from medicinal plants with antimicrobial activity are considered a promising alternative in the treatment of fungal infections. In this perspective, this study proposed to evaluate the antifungal activity of the dichloromethane fraction of Annona crassiflora Mart. against C. albicans strains. Tests were carried out to determine Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC), microbial growth kinetics, fungal cell wall and membrane mechanisms of action, antifungal biofilm activity, and cytotoxic effects on human erythrocytes. The extract presented MIC and MFC values that ranged from 256 µg/mL to 1,024 µg/mL, with fungicidal activity in the microbial growth kinetics assay. The mechanism of action did not occur through damage to the cell wall or via binding to ergosterol in the membrane, though the fraction presents activity against biofilm and is not cytotoxic in human erythrocytes. The dichloromethane fraction of Annonacrassiflora Mart. presented antifungal activity and reduced biofilm growth, without toxicity against human erythrocytes; however, further studies are needed to define its mechanism of action.
A síndrome da ardência bucal (SAB) enquadra-se como uma condição de origem multifatorial cuja etiologia do processo da doença é desconhecida, mas acredita-se que seja de origem neuropática. A literatura tem avaliado a eficácia de várias formas de tratamento para a SAB, seja com fármacos ou terapias não farmacológicas. Dentro do grupo das terapias farmacológicas, tem-se um fitofármaco emergente que vem demonstrando efeitos desejáveis no tratamento da SAB, a catuama®, já entre as terapias não farmacológicas, a que se destaca é a terapia com laser de baixa intensidade (TLBI). Com isso, o presente estudo objetivou realizar uma revisão de literatura acerca do potencial terapêutico da catuama® e da TLBI no tratamento da SAB. O referido estudo trata-se de uma revisão de literatura narrativa, na qual, para sua realização foram consultadas as bases de dados: Biblioteca Virtual em Saúde (BVS), Publicações Médicas (PubMed), Google Acadêmico, Medline e biblioteca virtual Scientific Eletronic Library Online (SCIELO). Para realizar tal busca foram utilizados os Descritores em Ciência da Saúde (DECS): Burning Mouth Syndrome, Low-Level Light Therapy e Phytotherapy, isoladamente e em conjunto, sendo assim, de acordo com os critérios de inclusão e exclusão estabelecidos, foram selecionadas 22 referências para a realização dessa revisão. Esse estudo evidencia que a literatura fundamenta tanto a catuama® quanto a TLBI como boas medidas terapêuticas no tratamento da SAB, porém, ensaios clínicos precisam ser realizados a fim de padronizar um protocolo seguro e prático do uso dessas terapias no tratamento dessa condição.