RESUMO
BACKGROUND: Sophorolipids are glycolipid biosurfactants with potential antibacterial, antifungal, and anticancer applications, rendering them promising for research. Therefore, this study hypothesizes that sophorolipids may have a notable impact on disrupting membrane integrity and triggering the production of reactive oxygen species, ultimately resulting in the eradication of pathogenic microbes. RESULTS: The current study resulted in the isolation of two Metschnikowia novel yeast strains. Sophorolipids production from these strains reached maximum yields of 23.24 g/l and 21.75 g/l, respectively, at the bioreactors level. Biosurfactants sophorolipids were characterized using FTIR and LC-MS techniques and found to be a mixture of acidic and lactonic forms with molecular weights of m/z 678 and 700. Our research elucidated sophorolipids' mechanism in disrupting bacterial and fungal membranes through ROS generation, confirmed by transmission electron microscopy and FACS analysis. The results showed that these compounds disrupted the membrane integrity and induced ROS production, leading to cell death in Klebsiella pneumoniae and Fusarium solani. In addition, the anticancer properties of sophorolipids were investigated on the A549 lung cancer cell line and found that sophorolipid-11D (SL-11D) and sophorolipid-11X (SL-11X) disrupted the actin cytoskeleton, as evidenced by immunofluorescence microscopy. The A549 cells were stained with Acridine orange/Ethidium bromide, which showed that they underwent necrosis. This was confirmed by flow cytometric analysis using Annexin/PI staining. The SL-11D and SL-11X molecules exhibited low levels of haemolytic activity and in-vitro cytotoxicity in HEK293, Caco-2, and L929 cell lines. CONCLUSION: In this work, novel yeast species CIG-11DT and CIG-11XT, isolated from the bee's gut, produce significant yields of sophorolipids without needing secondary oil sources, indicating a more economical production method. Our research shows that sophorolipids disrupt bacterial and fungal membranes via ROS production. They suggest they may act as chemo-preventive agents by inducing apoptosis in lung cancer cells, offering the potential for enhancing anticancer therapies.
Assuntos
Antifúngicos , Antineoplásicos , Metschnikowia , Estresse Oxidativo , Espécies Reativas de Oxigênio , Tensoativos , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/metabolismo , Humanos , Tensoativos/farmacologia , Tensoativos/metabolismo , Tensoativos/química , Estresse Oxidativo/efeitos dos fármacos , Antineoplásicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Metschnikowia/metabolismo , Metschnikowia/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Fusarium/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , Glicolipídeos/farmacologia , Glicolipídeos/metabolismo , Testes de Sensibilidade Microbiana , Ácidos OleicosRESUMO
In Candida albicans, Cdr1 pumps azole drugs out of the cells to reduce intracellular accumulation at detrimental concentrations, leading to azole-drug resistance. Milbemycin oxime, a veterinary anti-parasitic drug, strongly and specifically inhibits Cdr1. However, how Cdr1 recognizes and exports azole drugs, and how milbemycin oxime inhibits Cdr1 remain unclear. Here, we report three cryo-EM structures of Cdr1 in distinct states: the apo state (Cdr1Apo), fluconazole-bound state (Cdr1Flu), and milbemycin oxime-inhibited state (Cdr1Mil). Both the fluconazole substrate and the milbemycin oxime inhibitor are primarily recognized within the central cavity of Cdr1 through hydrophobic interactions. The fluconazole is suggested to be exported from the binding site into the environment through a lateral pathway driven by TM2, TM5, TM8 and TM11. Our findings uncover the inhibitory mechanism of milbemycin oxime, which inhibits Cdr1 through competition, hindering export, and obstructing substrate entry. These discoveries advance our understanding of Cdr1-mediated azole resistance in C. albicans and provide the foundation for the development of innovative antifungal drugs targeting Cdr1 to combat azole-drug resistance.
Assuntos
Antifúngicos , Azóis , Candida albicans , Microscopia Crioeletrônica , Proteínas Fúngicas , Proteínas de Membrana Transportadoras , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/antagonistas & inibidores , Antifúngicos/farmacologia , Antifúngicos/química , Azóis/farmacologia , Azóis/química , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/ultraestrutura , Farmacorresistência Fúngica , Fluconazol/farmacologia , Sítios de LigaçãoRESUMO
Ketoconazole (K) is a poorly water-soluble drug that faces significant challenges in achieving therapeutic efficacy. This study aimed to enhance the dissolution rate of ketoconazole by depositing spray-dried ketoconazole (SK) onto the surface of ground trehalose dihydrate (T) using spray drying. Ketoconazole-trehalose surface solid dispersions (SKTs) were prepared in ratios of 1:1 (SK1T1), 1:4 (SK1T4), and 1:10 (SK1T10), and characterized them using particle size analysis, scanning electron microscopy, powder X-ray diffraction, and in vitro dissolution studies. Results showed that the dissolution rates of the dispersions were significantly higher than those of pure ketoconazole, with the 1:10 ratio showing the highest dissolution rate. The improved dissolution was attributed to the formation of a new crystalline phase and better dispersion of ketoconazole particles. These findings suggest that the surface solid dispersion approach could be a valuable method for enhancing the bioavailability of poorly water-soluble drugs.
Assuntos
Cetoconazol , Tamanho da Partícula , Solubilidade , Trealose , Difração de Raios X , Cetoconazol/química , Cetoconazol/administração & dosagem , Trealose/química , Difração de Raios X/métodos , Microscopia Eletrônica de Varredura/métodos , Secagem por Atomização , Química Farmacêutica/métodos , Pós/química , Disponibilidade Biológica , Composição de Medicamentos/métodos , Antifúngicos/química , Antifúngicos/administração & dosagemRESUMO
Candida auris is a multidrug-resistant yeast that has seen a worrying increase during the COVID-19 pandemic. Give7/n this, new therapeutic options, such as controlled-release nanomaterials, may be promising in combating the infection. Therefore, this study aimed to develop amphotericin B (AmB) and micafungin (MICA)-loaded nanoemulsions (NEMA) and evaluated against biofilms of C. auris. Nanoemulsions (NEs) were characterized and determined minimum inhibitory concentration MIC90, checkerboard and anti-biofilm. NEMA presented a size of 53.7 and 81.4 nm for DLS and NTA, respectively, with good stability and spherical morphology. MICAmB incorporated efficiency was 88.4 and 99.3%, respectively. The release results show that AmB and MICA obtained a release of 100 and 63.4%, respectively. MICAmB and NEMA showed MIC90 values of 0.015 and 0.031 ug/mL, respectively and synergism. NEMA showed greater metabolic inhibition and morphological changes in mature biofilms. This drugs combination and co-encapsulation proved to be a promising therapy against C. auris biofilms.
Assuntos
Anfotericina B , Antifúngicos , Biofilmes , Candida auris , Emulsões , Micafungina , Testes de Sensibilidade Microbiana , Biofilmes/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/administração & dosagem , Anfotericina B/farmacologia , Anfotericina B/administração & dosagem , Anfotericina B/química , Micafungina/farmacologia , Micafungina/administração & dosagem , Emulsões/farmacologia , Emulsões/química , Candida auris/efeitos dos fármacos , Humanos , SARS-CoV-2/efeitos dos fármacos , COVID-19 , Nanopartículas/químicaRESUMO
Zinc oxide nanoparticles have wide range biological, biomedical and environmental applications. However, traditional nanofabrication of ZnONPs uses various toxic chemicals and organic solvents which limit their bio-applications. To overcome this hurdle, Bauhinia variegata derived buds extract was utilized to fabricate ZnONPs. The greenly generated ZnONPs were successfully prepared and extensively characterized using different analytical tools and the average crystalline size was calculated as 25.47 nm. Further, bioengineered ZnONPs were explored for multiple biological activities that revealed excellent therapeutic potentials. The antibacterial potential was determined using different bacterial strains. Pseudomonas aeruginosa (MIC: 137.5 µg/mL) was reported to be the most resistant variant while Bacillus subtilis (MIC: 34.38 µg/mL) was observed to be most susceptible bacterial strain. DPPH radical scavenging potential was measured to determine the antioxidant capacity of ZnONPs and the highest scavenging potential was observed as 82% at highest of 300 µg/mL. The fungicidal effect of green ZnONPs in comparison with Amphotericin B was assessed against five selected pathogenic fungal strains. The results revealed, Fusarium solani (MIC: 46.875 µg/mL) was least resistant and Aspergillus flavus (MIC: 187.5 µg/mL) was most resistant in fungicidal examination. Cytotoxicity potential of B.V@ZnONPs was analyzed against newly hatched nauplii of brine shrimps. The results for greenly produced ZnONPs was recorded as 39.78 µg/mL while 3.006 µg/mL was reported for positive control vincristine sulphate. The results confirmed the category of general cytotoxic for greenly synthesized nano sized B.V@ZnONPs.
Assuntos
Antibacterianos , Bauhinia , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Óxido de Zinco , Bauhinia/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Antioxidantes/farmacologia , Antioxidantes/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Animais , Química Verde/métodosRESUMO
Moringadepsin (6) and chaetone B (7) were isolated by us in the course of a conventional chemical screening of Morinagamyces vermicularis CBS 303.81, a fungus belonging to the relatively underexplored family Schizotheciaceae of the phylum Ascomycota. Since these metabolites did not account for the antifungal activity observed in a crude extract of this fungus, we utilized an MS/MS-based molecular networking approach to get a thorough insight into the secondary metabolites produced by this strain. Manual annotation of high-resolution fragmentation mass spectra by CANOPUS classified a major molecular family as putatively new thiodiketopiperazines. However, these results were opposite to the results of ChemWalker analysis based solely on MS/MS data, assigning these metabolites as various polyketides. Thus, targeted preparative HPLC isolation focusing on the most abundant features within this major molecular family resulted in the isolation of five secondary metabolites. Their structures were elucidated based on HRMS and NMR data as four new thiodiketopiperazine derivatives, botryosulfuranols D-G (1-4), alongside the known botryosulfuranol A (5). Compounds 1-3 and 5 exhibited moderate to weak antifungal activity against different test strains, accounting for the initial antifungal activity observed for its crude extract. Our study stressed the importance of full NMR-based structure elucidation for metabolomics research.
Assuntos
Ascomicetos , Estrutura Molecular , Ascomicetos/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Espectrometria de Massas em Tandem/métodos , Testes de Sensibilidade Microbiana , Policetídeos/farmacologia , Policetídeos/química , Policetídeos/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodosRESUMO
The discovery of a lead compound against Candida albicans is urgently needed because of the lack of clinically available antifungal drugs and the increase in drug resistance. Herein, a ß-carboline alkaloid methylaervine (MET) exhibited potential activity against C. albicans (MIC = 16-128 µg/mL), no hemolytic toxicity, and a low tendency to induce drug resistance. An antifungal mechanism study indicated that MET effectively inhibited the biofilm formation and disrupted the mature biofilm. Moreover, filamentation formation and spore germination were also weakened. The electron microscopy analysis revealed that MET could damage the cell structure, including the cell wall, membrane, and cytoplasm. In particular, the permeability and integrity of the cell membrane were destroyed. When it entered the fungi cell, it interfered with the redox homeostasis and DNA function. Overall, MET can inhibit the growth of C. albicans from multiple channels, such as biofilm, filamentation, cell structure, and intracellular targets, which are difficult to mutate at the same time to generate drug resistance. This work provides a promising lead compound for the creation of new antifungal agents against C. albicans.
Assuntos
Antifúngicos , Biofilmes , Candida albicans , Testes de Sensibilidade Microbiana , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Antifúngicos/farmacologia , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Carbolinas/farmacologia , Carbolinas/química , Membrana Celular/efeitos dos fármacosRESUMO
Fungal phytopathogens represent a large and economically significant challenge to food production worldwide. Thus, the application of biocontrol agents can be an alternative. In the present study, we carried out biological, metabolomic, and genetic analyses of three endophytic isolates from nodules of Chamaecytisus albus, classified as Pseudomonas chlororaphis acting as antifungal agents. The efficiency of production of their diffusible and volatile antifungal compounds (VOCs) was verified in antagonistic assays with the use of soil-borne phytopathogens: B. cinerea, F. oxysporum, and S. sclerotiorum. Diffusible metabolites were identified using chromatographic and spectrometric analyses (HPTLC, GC-MS, and LC-MS/MS). The phzF, phzO, and prnC genes in the genomes of bacterial strains were confirmed by PCR. In turn, the plant growth promotion (PGP) properties (production of HCN, auxins, siderophores, and hydrolytic enzymes, phosphate solubilization) of pseudomonads were bioassayed. The data analysis showed that all tested strains have broad-range antifungal activity with varying degrees of antagonism. The most abundant bioactive compounds were phenazine derivatives: phenazine-1-carboxylic acid (PCA), 2-hydroxy-phenazine, and diketopiperazine derivatives as well as ortho-dialkyl-aromatic acids, pyrrolnitrin, siderophores, and HCN. The results indicate that the tested P. chlororaphis isolates exhibit characteristics of biocontrol organisms; therefore, they have potential to be used in sustainable agriculture and as commercial postharvest fungicides to be used in fruits and vegetables.
Assuntos
Antifúngicos , Pseudomonas chlororaphis , Antifúngicos/farmacologia , Antifúngicos/química , Pseudomonas chlororaphis/metabolismo , Ascomicetos/metabolismo , Fusarium/efeitos dos fármacos , Fusarium/metabolismo , Botrytis/efeitos dos fármacos , Endófitos/metabolismo , Metabolômica/métodos , Compostos Orgânicos Voláteis/farmacologia , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/química , Fenazinas/metabolismo , Fenazinas/farmacologia , Fenazinas/química , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controleRESUMO
Two endophytes from the same Ginkgo biloba host were isolated and cultured separately. Three new eremophilane sesquiterpenoids (1-3), three new furan derivates (6, 8-9), one new polyketide (10), and four known compounds (4, 5, 7, 11) from Paraphaeosphaeria sp. and two new 10-membered macrolides (12-13), a new liner polyketide (14), a new benzofuran (15), and six known compounds (16-21) from Nigrospora oryzae were isolated. The structures of the isolated compounds were determined by spectroscopic methods, NMR calculations, and ECD calculations. The compounds 3-7, 9-10, 12, and 14-17 showed significant antiphytopathogenic effects against mycotoxigenic Alternaria sp. comparable to the activity of nystatin (positive control). Compounds 2, 6, 8, 9, and 18 indicated inhibitions against phytopathogen Fusarium asiaticum with MICs < 10 µg/mL. In addition, the compounds with weak antifungal activities from two endophytes were mixed to test their antifungal activity. The results showed that the metabolites from two endophytes had synergistic antifungal effects, and the beneficial interactions between natural products can induce more antifungal effects against plant pathogens than that of single compounds.
Assuntos
Ascomicetos , Endófitos , Ginkgo biloba , Doenças das Plantas , Endófitos/química , Endófitos/metabolismo , Ginkgo biloba/microbiologia , Ginkgo biloba/química , Ascomicetos/química , Ascomicetos/efeitos dos fármacos , Ascomicetos/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Estrutura Molecular , Fusarium/efeitos dos fármacos , Alternaria/efeitos dos fármacos , Alternaria/química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Antifúngicos/farmacologia , Antifúngicos/química , Testes de Sensibilidade MicrobianaRESUMO
Bryophyllum pinnatum is used to cure infections worldwide. Although the flavonoids of this plant are well known, it is still unknown how much of the plant's Ag and ZnO nanoparticles are beneficial. In the current research work, silver and zinc oxide nanoparticles were prepared using Bryophyllum pinnatum extract. The synthesized particles were characterized by UV-visible spectroscopy, SEM, EDS, XRD and FTIR. Synthesized particles were subjected to evaluation of their bactericidal and antifungal activity at various doses. Uv vis spectra at 400 nm corresponding to AgNPs confirmed their synthesis. Strong peaks in the EDS spectra of Ag and ZnO indicate the purity of the sample. The scanning electron microscopic images of ZnONPs showed a size of about 60 nm ± 3 nm, which demonstrated the presence of triangular-shaped ZnO nanoparticles. Green synthesized nanoparticles showed bactericidal activity against both Gram-positive (Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Agrobacterium tumifaciens, Salmonella setubal, Enterobacter aerogenes) strains. AgNPs proved to be more effective against Gram-negative bacterial strains compared to Gram-positive owing to MIC values (10 ppm and 20 ppm respectively). Whereas, ZnONPs were found more effective against Gram-positive bacteria with lower MIC values (10 ppm) as compared to Gram-negative ones (20 ppm). Also, the synthesized nanoparticles exhibited moderate dose-dependent antifungal activity against tested fungal strains ranging from 10 to 70%. Cytotoxicity of nanoparticles was found significant using Brine shrimp's lethality assay with IC50 values of 4.09 ppm for AgNPs, 13.72 ppm for ZnONPs, and 24.83 ppm for plant extract. Conclusively, Ag and ZnO nanoparticles were more effective than plant extract and AgNPs had higher activities than those of ZnONPs. Further research is warranted to explore the precise mechanism of action and the potential applications of these nanoparticles in the medical field.
Assuntos
Kalanchoe , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Prata , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Nanopartículas Metálicas/química , Kalanchoe/química , Prata/química , Prata/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antifúngicos/farmacologia , Antifúngicos/química , Artemia/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacosRESUMO
The fungus Malassezia globosa is often responsible for superficial mycoses posing significant treatment challenges because of the unfavourable side effects of available antifungal drugs. To reduce potential hazards to the host and overcome these hurdles, new therapeutic medicines must be developed that selectively target enzymes unique to the pathogen. This study focuses on the enzyme anthranilate phosphoribosyltransferase (AnPRT), which is vital to M. globosa's tryptophan production pathway. To learn more about the function of the AnPRT enzyme, we modeled, validated, and simulated its structure. Moreover, many bioactive components were found in different extracts from the plant Albizia amara after phytochemical screening. Interestingly, at doses ranging from 500 to 2000 µg/ml, the chloroform extract showed significant antifungal activity, with inhibition zones measured between 11.0 ± 0.0 and 25.6 ± 0.6 mm. According to molecular docking analyses, the compounds from the active extract, particularly 2-tert-Butyl-4-isopropyl-5-methylphenol, interacted with the AnPRT enzyme's critical residues, ARG 205 and PHE 214, with an effective binding energy of -4.9 kcal/mol. The extract's revealed component satisfies the requirements for drug-likeness and shows promise as a strong antifungal agent against infections caused by M. globosa. These findings imply that using plant-derived chemicals to target the AnPRT enzyme is a viable path for the creation of innovative antifungal treatments.
Assuntos
Albizzia , Antranilato Fosforribosiltransferase , Antifúngicos , Malassezia , Albizzia/química , Antranilato Fosforribosiltransferase/metabolismo , Antranilato Fosforribosiltransferase/química , Antifúngicos/farmacologia , Antifúngicos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Proteínas Fúngicas/metabolismo , Malassezia/efeitos dos fármacos , Malassezia/enzimologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
Fungal diseases could severely harm agricultural productions. To develop new antifungal agents, based on the Global Natural Products Social Molecular Networking, typical bromine isotope peak ratios, and ultraviolet absorptions, cultivation of the soft coral-derived endophytic fungi Aspergillus terreus EGF7-0-1 with NaBr led to the targeted isolation of 14 new brominated aromatic butenolides (1-14) and six known analogues (15-20). Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1-14 exhibited wildly antifungal activities (against Colletotrichum gloeosporioides, Pestalotiopsis microspora, Fusarium oxysporum f. sp. cubense, Botrytis cinerea, and Diaporthe phoenicicola). The bioassay results showed that compounds 1-14 exhibited excellent antifungal activities against C. gloeosporioides, with concentration for 50% of maximal effect (EC50) values from 2.72 to 130.41 nM. The mechanistic study suggests that compound 1 may disrupt nutrient signaling pathways by reducing the levels of metabolites, such as carbohydrates, lipids, and amino acids, leading to an increase in low-density granules and a decrease in high-density granules in the cytoplasm, accompanied by numerous vacuoles, thereby inhibiting the growth of C. gloeosporioides. Monobrominated γ-butenolide 1 may be expected to exploit a novel agriculturally antifungal leading drug. Meanwhile, compound M1 has conformed antifugual activities against C. gloeosporioides by papayas in vivo.
Assuntos
4-Butirolactona , Aspergillus , Fungicidas Industriais , Aspergillus/metabolismo , Aspergillus/efeitos dos fármacos , Aspergillus/química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Estrutura Molecular , Colletotrichum/efeitos dos fármacos , Halogenação , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Antifúngicos/químicaRESUMO
Microalgae are of great interest due to their ability to produce valuable compounds, such as pigments, omega-3 fatty acids, antioxidants, and antimicrobials. The dinoflagellate genus Amphidinium is particularly notable for its amphidinol-like compounds, which exhibit antibacterial and antifungal properties. This study utilized a two-stage cultivation method to grow Amphidinium carterae CCAP 1102/8 under varying conditions, such as blue LED light, increased salinity, and the addition of sodium carbonate or hydrogen peroxide. After cultivation, the biomass was extracted and fractionated using solid-phase extraction, yielding six fractions per treatment. These fractions were analyzed using Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS/MS) to identify their chemical components. Key amphidinol compounds (AM-B, AM-C, AM-22, and AM-A) were identified, with AM-B being the most abundant in Fraction 4, followed by AM-C. Fraction 5 also contained a significant amount of AM-C along with an unknown compound. Fraction 4 returned the highest antimicrobial activity against the pathogens Staphylococcus aureus, Enterococcus faecalis, and Candida albicans, with Minimal Biocidal Concentrations (MBCs) ranging from 1 to 512 µg/mL. Results indicate that the modulation of both amphidinol profile and fraction bioactivity can be induced by adjusting the cultivation parameters used to grow two-stage batch cultures of A. carterae.
Assuntos
Candida albicans , Dinoflagellida , Testes de Sensibilidade Microbiana , Dinoflagellida/química , Dinoflagellida/crescimento & desenvolvimento , Dinoflagellida/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Antibacterianos/farmacologia , Antibacterianos/química , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Cromatografia Líquida , Antifúngicos/farmacologia , Antifúngicos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , AnfidinóisRESUMO
Aspergillus carbonarius, a common food-contaminating fungus, produces ochratoxin A (OTA) and poses a risk to human health. This study aimed to assess the inhibitory activity of tea tree essential oil and its main components, Terpene-4-ol (T4), α-terpineol (αS), and 3-carene (3C) against A. carbonarius. The study showed αS and T4 were the main antifungal components of tea tree essential oil, which primarily inhibit A. carbonarius growth through cell membrane disruption, reducing antioxidant enzyme activities (catalase, peroxidase, superoxide dismutase) and interrupting the tricarboxylic acid cycle. Furthermore, αS and T4 interacted with enzymes related to OTA biosynthesis. Molecular docking and molecular dynamics show that they bound mainly to P450 with a minimum binding energy of -7.232 kcal/mol, we infered that blocking the synthesis of OTA precursor OTß. Our hypothesis was preliminarily verified by the detection of key substances in the OTA synthesis pathway. The results of UHPLC-QTOF-MS2 analysis demonstrated that T4 achieved a degradation rate of 43 % for OTA, while αS reached 29.6 %, resulting in final breakdown products such as OTα and phenylalanine. These results indicated that α-terpinol and Terpene-4-ol have the potential to be used as naturally safe and efficient preservatives or active packaging to prevent OTA contamination.
Assuntos
Aspergillus , Monoterpenos Cicloexânicos , Simulação de Acoplamento Molecular , Ocratoxinas , Terpenos , Ocratoxinas/metabolismo , Ocratoxinas/biossíntese , Aspergillus/metabolismo , Aspergillus/efeitos dos fármacos , Terpenos/metabolismo , Óleo de Melaleuca/farmacologia , Óleo de Melaleuca/química , Monoterpenos/farmacologia , Monoterpenos/metabolismo , Antifúngicos/farmacologia , Antifúngicos/química , Monoterpenos BicíclicosRESUMO
As an important small organic molecule, cyclopropane is widely used in drug design. In this paper, fifty-three amide derivatives containing cyclopropane were designed and synthesized by introducing amide groups and aryl groups into cyclopropane through the active splicing method, and their antibacterial and antifungal activities were evaluated in vitro. Among them, thirty-five compounds were new compounds, and eighteen compounds were known compounds (F14, F15, F18, F20-F26, F36, and F38-F44). Bioassay results disclosed that four, three, and nine of the compounds showed moderate activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, respectively. Three compounds were sensitive to Candida albicans, with excellent antifungal activity (MIC80 = 16 µg/mL). The molecular docking results show that compounds F8, F24, and F42 have good affinity with the potential antifungal drug target CYP51 protein.
Assuntos
Amidas , Antifúngicos , Candida albicans , Ciclopropanos , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Staphylococcus aureus , Ciclopropanos/farmacologia , Ciclopropanos/química , Ciclopropanos/síntese química , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Candida albicans/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Escherichia coli/efeitos dos fármacos , Relação Estrutura-Atividade , Anti-Infecciosos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Estrutura MolecularRESUMO
Silver nanoparticles (AgNPs) synthesized from plant extracts have gained attention for their potential applications in biomedicine. Calotropis gigantea has been utilized to synthesize AgNPs, called AgNPs-LCg, and exhibit antibacterial activities against both Gram-positive and Gram-negative bacteria as well as antifungal. However, further enhancement of their antimicrobial properties is needed. The aim of this study was to synthesize AgNPs-LCg and to enhance their antimicrobial and antifungal activities through a hybrid green synthesis reaction using patchouli oil (PO), as well as to characterize the synthesized AgNPs-LCg. Optimization was conducted using the response surface method (RSM) with a central composite design (CCD). AgNPs-LCg were synthesized under optimal conditions and hybridized with different forms of PO-crude, distillation wastewater (hydrolate), and heavy and light fractions-resulting in PO-AgNPs-LCg, PH-AgNPs-LCg, LP-AgNPs-LCg, and HP-AgNPs-LCg, respectively. The samples were then tested for their antibacterial (both Gram-positive and Gram-negative bacteria) and antifungal activities. Our data indicated that all samples, including those with distillation wastewater, had enhanced antimicrobial activity. HP-AgNPs-LCg, however, had the highest efficacy; therefore, only HP-AgNPs-LCg proceeded to the characterization stage for comparison with AgNPs-LCg. UV-Vis spectrophotometry indicated surface plasmon resonance (SPR) peaks at 400 nm for AgNPs-LCg and 360 nm for HP-AgNPs-LCg. The Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of O-H, N-H, and C-H groups in C. gigantea extract and AgNP samples. The smallest AgNPs-LCg were 56 nm, indicating successful RSM optimization. Scanning electron microscopy (SEM) analysis revealed spherical AgNPs-LCg and primarily cubic HP-AgNPs-LCg, with energy-dispersive X-ray spectroscopy (EDX) confirming silver's predominance. This study demonstrated that PO in any form significantly enhances the antimicrobial properties of AgNPs-LCg. The findings pave the way for the exploration of enhanced and environmentally sustainable antimicrobial agents, capitalizing on the natural resources found in Aceh Province, Indonesia.
Assuntos
Calotropis , Química Verde , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Folhas de Planta , Prata , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Química Verde/métodos , Folhas de Planta/química , Calotropis/química , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Óleos de Plantas/farmacologia , Óleos de Plantas/químicaRESUMO
INTRODUCTION AND OBJECTIVE: Medicinal plants have a long and significant history of being used for their healing properties. One famous example is Commiphora, which is mostly found in the southern part of Arabia. The objective of this study was to evaluate the effectiveness of a water-based extract obtained from two different varieties of myrrh in suppressing the proliferation of Candida spp. at different concentrations. MATERIAL AND METHODS: The inhibitory activity of the aqueous extract of two different varieties of myrrh, commonly used in traditional medicine, was assessed against five pathogenic yeasts using the diffusion technique. Mass spectrum was used to analyze myrrh's chemical composition for antimicrobial effects. RESULTS: The aqueous extract of both tested species of myrrh (Commiphora myrrha and Commiphora molmol) showed inhibitory effects on all tested isolates. During the chemical examination of myrrh, it was noted that the material included 12 components known for their antimicrobial properties. The essential oil derived from two varieties of myrrh showed the most significant effects on Candida tropicalis (ATCC 66029), Candida guilliermondii (ATCC 6260), Candida laurentii (ATCC 18803), Candida neoformans (ATCC 66031), and Candida albicans (ATCC 14053). Analysis of chemical composition of the myrrh revealed 19 known components, of which 12 compounds have been proven by research to suppress the growth of microorganisms. CONCLUSIONS: C. myrrha and C. molmol aqueous extracts exhibit a promising antifungal effect against common Candida infections. The aqueous extracts present a variety of antimicrobial compounds; however, further research is necessary to elucidate the specific mechanisms of action of these compounds, and to evaluate their efficacy, toxicity and safety before considering their clinical application.
Assuntos
Antifúngicos , Candida , Commiphora , Resinas Vegetais , Antifúngicos/farmacologia , Antifúngicos/química , Commiphora/química , Candida/efeitos dos fármacos , Resinas Vegetais/química , Resinas Vegetais/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Testes de Sensibilidade Microbiana , Terpenos/farmacologia , Terpenos/química , Óleos Voláteis/farmacologia , Óleos Voláteis/químicaRESUMO
The widespread and irrational use of azole antifungal agents has led to an increase of azole-resistant Candida albicans strains with an urgent need for combination drug therapy, enhancing the treatment efficacy. Here, we report the discovery of a first-in-class pyrazole-isoxazole, namely, 5b, that showed remarkable growth inhibition against the C. albicans ATCC 10231 strain in combination with voriconazole, acting as a downregulator of ERG 11 (Cyp51) gene expression with a significant reduction of the yeast-to-hypha morphological transition. Furthermore, C. albicans CYP51 enzyme assay and in-depth molecular docking studies unveiled the unique ability of the combination of 5b and voriconazole to completely fill the CYP51 binding sites. In vivo studies using a Galleria mellonella model confirmed the previously in vitro observed synergistic effect of 5b with voriconazole. Also considering its biocompatibility in a cellular model of human keratinocytes, these results indicate that 5b represents a promising compound for a further optimization campaign.
Assuntos
Antifúngicos , Candida albicans , Farmacorresistência Fúngica , Isoxazóis , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Pirazóis , Voriconazol , Antifúngicos/farmacologia , Antifúngicos/química , Voriconazol/farmacologia , Candida albicans/efeitos dos fármacos , Pirazóis/farmacologia , Pirazóis/química , Animais , Humanos , Isoxazóis/farmacologia , Isoxazóis/química , Sinergismo Farmacológico , Mariposas/microbiologia , Mariposas/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Modelos Animais de Doenças , Relação Estrutura-Atividade , Azóis/farmacologia , Azóis/química , Azóis/uso terapêuticoRESUMO
In this work, chitosan was combined with bio-vanillin (BV) and kaolin clay (KC) to create a novel antifungal and biodegradable food packaging film. The chitosan/KC/BV film exhibited an antioxidant capacity of 80 % as measured by DPPH assay, which was significantly higher than that of the chitosan film which has 55.6 %). The film also demonstrated strong antimicrobial activity with a reduction of 90 % in the growth of E. coli and S. aureus compared to the control. Additionally, the chitosan/KC/BV film showed a 75 % reduction in fungal growth compared to chitosan film. Furthermore, the water vapor permeability of the chitosan film was reduced as 5.38 with the addition of KC/BV. The degradation study revealed that the chitosan/KC film degraded by 88 % within 20 days under composting conditions. Additionally, fresh-cut apple slices were used to examine the effectiveness of chitosan/KC/BV film as a packaging material. The fruit's weight loss and browning index showed satisfactory food preservation. Our research suggests that the chitosan/KC/BV film has great potential for use in the food sector due to its strong antioxidant, antimicrobial, and biodegradable properties.
Assuntos
Antibacterianos , Antifúngicos , Antioxidantes , Benzaldeídos , Quitosana , Embalagem de Alimentos , Caulim , Quitosana/química , Quitosana/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Embalagem de Alimentos/métodos , Benzaldeídos/química , Benzaldeídos/farmacologia , Caulim/química , Caulim/farmacologia , Argila/química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacologia , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Escherichia coli , Staphylococcus aureusRESUMO
With the emergence of multidrug-resistant microorganisms, microbial agents have become a serious global threat, affecting human health and various plants. Therefore, new therapeutic alternatives, such as chitin-binding proteins, are necessary. Chitin is an essential component of the fungal cell wall, and chitin-binding proteins exhibit antifungal activity. In the present study, chitin-binding peptides isolated from Capsicum chinense seeds were characterized and evaluated for their in vitro antimicrobial effect against the growth of Candida and Fusarium fungi. Proteins were extracted from the seeds and subsequently the chitin-binding proteins were separated by chitin affinity chromatography. After chromatography, two fractions, Cc-F1 (not retained on the column) and Cc-F2 (retained on the column), were obtained. Electrophoresis revealed major protein bands between 6.5 and 26.6 kDa for Cc-F1 and only a ~ 6.5 kDa protein band for Cc-F2, which was subsequently subjected to mass spectrometry. The protein showed similarity with hevein-like and endochitinase and was then named Cc-Hev. Data are available via ProteomeXchange with identifier PXD054607. Next, we predicted the three-dimensional structure of the peptides and performed a peptide docking with (NAG)3. Subsequently, growth inhibition assays were performed to evaluate the ability of the peptides to inhibit microorganism growth. Cc-Hev inhibited the growth of C. albicans (up to 75% inhibition) and C. tropicalis (100% inhibition) and induced a 65% decrease in cell viability for C. albicans and 100% for C. tropicalis. Based on these results, new techniques to combat fungal diseases could be developed through biotechnological applications; therefore, further studies are needed.