RESUMO
We evaluated by comparing the performance of three pneumatically-driven bioreactors in the production of L-asparaginase (L-ASNase), an enzyme used to treat leukaemia and lymphoma. A two-step screening process was conducted to detect Cunninghamella spp. strains producing L-ASNase. Cunninghamella echinulata DSM1905 produced the highest levels of L-ASNase during screening assays. Subsequently, fermentations were performed in bubble column (BCR), airlift (ALR), and hybrid fixed-bed airlift (FB-ALR) bioreactors to determine the best upstream bioprocess. Mycelial biomass production was higher in BCR than in ALR and FB-ALR (p ≤ 0.0322). The activity of L-ASNase produced in FB-ALR, in which the fungus grew as a consistent biofilm, was significantly higher (p ≤ 0.022) than that from ALR, which was higher than that of BCR (p = 0.036). The specific activity of ALR and FB-ALR presented no differences (p = 0.073), but it was higher than that of BCR (p ≤ 0.032). In conclusion, C. echinulata DSM1905, grown under the biofilm phenotype, produced the highest levels of L-ASNase, and FB-ALR was the best upstream system for enzyme production.
Assuntos
Asparaginase , Biofilmes , Reatores Biológicos , Cunninghamella , Reatores Biológicos/microbiologia , Cunninghamella/metabolismo , Biofilmes/crescimento & desenvolvimento , Asparaginase/biossíntese , Asparaginase/metabolismo , Fermentação , BiomassaRESUMO
Mucormycosis is receiving much more attention because of its high morbidity and extremely high mortality rate in immunosuppressed populations. In this study, we isolated a Cunnignhamella bertholletiae Z2 strain from a skin lesion of a 14â¯year, 9â¯months old girl with acute lymphoblastic leukemia who die of infection from the Z2 strain. Genome sequencing was performed after isolation and amplification of the Z2 strain to reveal potential virulence factors and pathogenic mechanisms. The results showed that the genome size of the Z2 strain is 30.9â¯Mb with 9213 genes. Mucoral specific virulence factor genes found are ARF, CalN, and CoTH, while no gliotoxin biosynthesis gene cluster was found, which is a known virulence factor in Aspergillus fumigatus adapted to the environment. The Z2 strain was found to have 69 cytochrome P450 enzymes, which are potential drug resistant targets. Sensitivity testing of Z2 showed it was only inhibited by amphotericin B and posaconazole. Detailed genomic information of the C. bertholletiae Z2 strain may provide useful data for treatment.
Assuntos
Antifúngicos , Cunninghamella , Sistema Enzimático do Citocromo P-450 , Genoma Fúngico , Mucormicose , Sistema Enzimático do Citocromo P-450/genética , Mucormicose/microbiologia , Feminino , Humanos , Cunninghamella/genética , Antifúngicos/farmacologia , Adolescente , Fatores de Virulência/genética , Sequenciamento Completo do Genoma , Filogenia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
We described a 14-year-old girl with acute lymphoblastic leukemia who developed disseminated mucormycosis during induction therapy. Disseminated Cunninghamella elegans infection was confirmed by histopathology, microbiological culture, and metagenomic next-generation sequencing analysis of skin tissue, blood, and cerebrospinal fluid. Subsequently, the patient received a combination of liposomal amphotericin B, posaconazole, and caspofungin for antifungal treatment, but eventually died because of severe fungal pneumonia, respiratory failure, and septic shock. Moreover, case reports of pulmonary mucormycosis in children published since 1959 were reviewed. In summary, metagenomic next-generation sequencing is an effective diagnostic method for Cunninghamella with high speed and sensitivity.
Assuntos
Cunninghamella , Mucormicose , Leucemia-Linfoma Linfoblástico de Células Precursoras , Feminino , Humanos , Criança , Adolescente , Mucormicose/tratamento farmacológico , Quimioterapia de Indução , Antifúngicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
We report a case of mucormycosis induced by Cunninghamella spp. infection in a ten-year-old girl with acute lymphoblastic leukemia, who developed fever and respiratory symptoms after chemotherapy and was diagnosed with invasive fungal disease. Peripheral blood DNA sequences were analyzed using metagenomic next-generation sequencing (mNGS), and by comparison with the Pathogens Metagenomics Database (PMDB), we identified Cunninghamella spp. with sequence number 514 as the pathogen. The patient was treated with amphotericin B combined with posaconazole and showed a favorable response. We searched Pubmed, Embase, CNKI, and Wanfang database for reports of cases of Cunninghamella spp. infection in children and retrieved 22 reported cases (including 12 males) with a median age of 13.5 (3-18) years. In these 22 cases, hematological malignancy was the most common underlying condition (19/22), and most of patients experienced an acute onset and rapid progression with respiratory symptoms (14/20) and fever (16/20) as the most common symptoms. CT imaging often showed unilateral lesions with varying imaging findings, including pulmonary nodules or masses, infiltrative changes, and pleural effusion. Definite diagnoses were established in 18 of the cases, and 4 had probable diagnoses; the lungs and skin were the most frequent organs compromised by the infection. A definite diagnosis of Cunninghamella spp. infection still relied on histopathological examination and fungal culture, but the molecular techniques including PCR and mNGS had shown potentials in the diagnosis. Almost all the cases received antifungal treatment after diagnosis (21/22), and 13 patients also underwent surgeries. Death occurred in 9 (42%) of the cases at a median of 19 (4-54) days after onset of the signs or symptoms. The patients receiving antifungal therapy combined with surgery had a high survival rate (9/13, 69%) than those with antifungal therapy alone (3/8, 37%). Invasive fungal disease is a common complication in immunoco-mpromised patients, but Cunninghamella spp. infection is rare and has a high mortality rate. In cases highly suspected of this disease, active diagnosis and early treatment are critical to improve the survival outcomes of the patients.
Assuntos
Cunninghamella , Mucormicose , Adolescente , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criança , Feminino , Humanos , Masculino , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/etiologiaRESUMO
Candida species are responsible for causing invasive candidiasis with high mortality rate and their resistance to available antifungal drugs is a major clinical challenge. Biotransformation process of the labdane diterpene ent-labd-8(17)-en-15,18-dioic acid (1) carried out with Cunninghamella elegans afforded five new derivatives (compounds 2-6). Unusual regioselective hydroxylation of the methyl group at the C-20 position of labdane-type diterpene was achieved and all compounds were subjected to cytotoxicity and antifungal evaluations. Compound 1 and its derivatives were not cytotoxic to normal (MCF-10A) and tumor (MCF-7) cell lines. Compounds 2 and 3 exhibited fungistatic activity against all tested Candida strains at lower concentrations than fluconazole. Both compounds also showed the strongest fungicidal activity against C.â albicans, which is the most prevalent fungal agent involved in candidemia.
Assuntos
Candida , Diterpenos , Antifúngicos/farmacologia , Biotransformação , Candida/metabolismo , Cunninghamella , Diterpenos/metabolismo , Diterpenos/farmacologia , Fluconazol , Testes de Sensibilidade MicrobianaRESUMO
We present the unusual case of a 60-year-old immunocompetent woman with chronic obstructive pulmonary disease who developed a necrotising pneumonia with isolation of Cunninghamella bertholletiae, Aspergillus niger, Staphylococcus pseudintermedius and adenovirus. The patient recovered with antimicrobial therapy and supportive care in the intensive care unit. The current literature on diagnosis and treatment of these pathogens is reviewed.
Assuntos
Mucormicose , Pneumonia Necrosante , Adenoviridae , Aspergillus niger , Cunninghamella , Feminino , Humanos , Pessoa de Meia-Idade , StaphylococcusRESUMO
AIMS: The objective of this study was to determine the best conditions to produce invertase by Cunninghamella echinulata PA3S12MM and to immobilize and apply the enzyme. METHODS AND RESULTS: The maximum production was verified in 8 days of cultivation at 28°C supplemented with 10 g L-1 apple peel, reaching 1054.85 U ml-1 . The invertase was purified from the DEAE-Sephadex column. The derivative immobilized in alginate-gelatin-calcium phosphate showed reusability >50% for 19 cycles. The derivative immobilized in glutaraldehyde-chitosan showed greater thermostability and at a different pH. The hydrolysis of 15 ml of sucrose 500 g L-1 in a fixed bed reactor (total volume of 31 ml) produced 24.44 µmol min-1 of glucose and fructose at a residence time of 30 min and a conversion factor of 0.5. CONCLUSIONS: The new wild strain C. echinulata PA3S12MM presents high invertase production in medium supplemented with an agro-industrial residue and the immobilized enzyme showed high thermal stability and resistance at a different pH. SIGNIFICANCE AND IMPACT OF THE STUDY: The fungus C. echinulata PA3S12MM is an excellent producer of invertases in Vogel medium supplemented with apple peel. The enzyme is promising for industrial application since it has good performance in reusability and inverted sugar production.
Assuntos
Cunninghamella , beta-Frutofuranosidase , Cunninghamella/metabolismo , Estabilidade Enzimática , Enzimas Imobilizadas , Frutose , Concentração de Íons de Hidrogênio , Temperatura , beta-Frutofuranosidase/metabolismoRESUMO
Pulmonary mucormycosis and aspergillosis with disseminated mucormycosis involving gastrointestinalin is a very rare but lethal infection leading to extreme mortality. Herein, we present a unique case of pulmonary coinfection with Cunninghamella bertholletiae and Aspergillus flavus, with disseminated mucormycosis involving the jejunum caused by C. bertholletiae in an acute B-lymphocytic leukemia (B-ALL) patient with familial diabetes. Early administration of active antifungal agents at optimal doses and complete resection of all infected tissues led to improved therapeutic outcomes.
Assuntos
Coinfecção , Cunninghamella , Pneumopatias , Mucormicose , Leucemia-Linfoma Linfoblástico de Células Precursoras , Aspergilose Pulmonar , Antifúngicos/uso terapêutico , Cunninghamella/fisiologia , Feminino , Humanos , Pneumopatias/microbiologia , Pessoa de Meia-Idade , Mucormicose/complicações , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Aspergilose Pulmonar/complicações , Resultado do TratamentoRESUMO
Animal chitosan (Chit-A) is gaining more acceptance in daily activities. It is used in a range of products from food supplements for weight loss to even raw materials for producing nanoparticles and hydrogel drug carriers; however, it has low antioxidant activity. Fungal oligochitosan (OChit-F) was identified as a potential substitute for Chit-A. Cunninghamella elegans is a fungus found in the Brazilian savanna (Caatinga) that produces OligoChit-F, which is a relatively poorly studied compound. In this study, 4 kDa OChit-F with a 76% deacetylation degree was extracted from C. elegans. OChit-F showed antioxidant activity similar to that of Chit-A in only one in vitro test (copper chelation) but exhibited higher activity than that of Chit-A in three other tests (reducing power, hydroxyl radical scavenging, and iron chelation). These results indicate that OChit-F is a better antioxidant than Chit-A. In addition, Chit-A significantly increased the formation of calcium oxalate crystals in vitro, particularly those of the monohydrate (COM) type; however, OChit-F had no effect on this process in vitro. In summary, OChit-F had higher antioxidant activity than Chit-A and did not induce the formation of CaOx crystals. Thus, OChit-F can be used as a Chit-A substitute in applications affected by oxidative stress.
Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Quitosana/química , Quitosana/farmacologia , Cunninghamella/metabolismo , Oligossacarídeos/biossíntese , Oligossacarídeos/farmacologia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Oxalato de Cálcio/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
A 42-year-old man diagnosed with acute myeloid leukemia complained of progressive swelling of the right side of his face with pain 11 days after the third cycle of consolidation therapy with high-dose arabinosylcytosine-cytarabine. Head and neck magnetic resonance imaging showed a mass lesion in his right maxillary sinus with parapharyngeal involvement, which included the right masseter muscle, intraorbital involvement, and an abscess in his brain. Chest computed tomography revealed peribronchial small nodules in his right upper lobe and a necrotic tumor in his right lower lobe. Molds identified as Cunninghamella bertholletiae were isolated from the necrotic ulcer. According to these results, chemotherapy for leukemia was discontinued. High-dose liposomal amphotericin (10 mg/kg/day) was initiated. Because renal dysfunction occurred, the dosage was decreased to 6 mg/kg and combined with 150 mg/day micafungin. Debridement of necrotic tissue in the right maxillary sinus and establishment of the fenestration between the sinus and oral cavity were performed. Subsequently, brain and lung lesions were surgically removed. Rhinocerebral mucormycosis was successfully treated without relapse over 3 years by a 112-day course of intravenous anti-fungal therapy and 223-day course of terbinafine and partial surgical removal, respectively, to maintain masticatory and ocular functions. To our knowledge, there has been no other report of a long-term survival case of rhinocerebral mucormycosis due to C. bertholletiae.
Assuntos
Infecções Fúngicas do Sistema Nervoso Central , Cunninghamella , Leucemia Mieloide Aguda , Pneumopatias Fúngicas , Mucormicose , Adulto , Antifúngicos/uso terapêutico , Antineoplásicos/uso terapêutico , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Pulmão/patologia , MasculinoRESUMO
Fatty acid amides (FAAs) are of great interest due to their broad industrial applications. They can be synthesized enzymatically with many advantages over chemical synthesis. In this study, the fatty acid moieties of lipids of Cunninghamella echinulata ATHUM 4411, Umbelopsis isabellina ATHUM 2935, Nannochloropsis gaditana CCAP 849/5, olive oil, and an eicosapentaenoic acid (EPA) concentrate were converted into their fatty acid methyl esters and used in the FAA (i.e., ethylene diamine amides) enzymatic synthesis, using lipases as biocatalysts. The FAA synthesis, monitored using in situ NMR, FT-IR, and thin-layer chromatography, was catalyzed efficiently by the immobilized Candida rugosa lipase. The synthesized FAAs exhibited a significant antimicrobial activity, especially those containing oleic acid in high proportions (i.e., derived from olive oil and U. isabellina oil), against several human pathogenic microorganisms, insecticidal activity against yellow fever mosquito, especially those of C. echinulata containing gamma-linolenic acid, and anticancer properties against SKOV-3 ovarian cancer cell line, especially those containing EPA in their structures (i.e., EPA concentrate and N. gaditana oil). We conclude that FAAs can be efficiently synthesized using microbial oils of different fatty acid composition and used in specific biological applications.
Assuntos
Amidas/metabolismo , Cunninghamella/metabolismo , Ácido Eicosapentaenoico/biossíntese , Fungos/metabolismo , Azeite de Oliva/metabolismo , Saccharomycetales/metabolismoRESUMO
The fungal transformations of medroxyrogesterone (1) were investigated for the first time using Cunninghamella elegans, Trichothecium roseum, and Mucor plumbeus. The metabolites obtained are as following: 6ß, 20-dihydroxymedroxyprogesterone (2), 12ß-hydroxymedroxyprogesterone (3), 6ß, 11ß-dihydroxymedroxyprogesterone (4), 16ß-hydroxymedroxyprogesterone (5), 11α, 17-dihydroxy-6α-methylpregn-4-ene-3, 20-dione (6), 11-oxo-medroxyprogesterone (7), 6α-methyl-17α-hydroxypregn-1,4-diene-3,20-dione (8), and 6ß-hydroxymedroxyprogesterone (9), 15ß-hydroxymedroxyprogesterone (10), 6α-methyl-17α, 11ß-dihydroxy-5α-pregnan-3, 20-dione (11), 11ß-hydroxymedroxyprogesterone (12), and 11α, 20-dihydroxymedroxyprogesterone (13). Among all the microbial transformed products, the newly isolated biotransformed product 13 showed the most potent activity against proliferation of SH-SY5Y cells. Compounds 12, 5, 6, 9, 11, and 3 (in descending order of activity) also showed some extent of activity against SH-SY5Y tumour cell line. The never been reported biotransformed product, 2, showed the most potent inhibitory activity against acetylcholinesterase. Molecular modelling studies were carried out to understand the observed experimental activities, and also to obtain more information on the binding mode and the interactions between the biotransformed products, and enzyme.
Assuntos
Proliferação de Células/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Medroxiprogesterona/farmacologia , Animais , Biotransformação , Caenorhabditis elegans/metabolismo , Inibidores da Colinesterase/química , Simulação por Computador , Cunninghamella/metabolismo , Hypocreales/metabolismo , Técnicas In Vitro , Medroxiprogesterona/química , Medroxiprogesterona/farmacocinética , Simulação de Acoplamento Molecular , Análise Espectral/métodosRESUMO
Biotransformation of an orally active contraceptive drug, desogestrel (1), with Cunninghamella elegans yielded a new metabolite, 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3,6-dione (2), along with five known metabolites, i.e., 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3ß,6ß,17ß-triol (3), 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6ß,17ß-diol-3-one (4), 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3-one (5), 13ß-ethyl-11-epoxy-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3-one (6), and 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-10ß,17ß-diol-3-one (7). The structure of new metabolite 2 was elucidated by using 1H-, 13C-, and 2D-NMR, EI-, and HREI-MS, IR, and UV spectroscopic data. Compounds 1-7 were evaluated for anti-inflammatory activities, i.e., inhibition of T-cell proliferation, and pro-inflammatory cytokine (TNF-α). Compounds 1 (IC50 = 1.12 ± 0.03 µg/mL), 2 (IC50 = 1.15 ± 0.05 µg/mL), 3 (IC50 = 1.15 ± 0.05 µg/mL), 4 (IC50 = 1.40 ± 0.03 µg/mL), 5 (IC50 = 1.78 ± 0.08 µg/mL), and 6 (IC50 = 1.36 ± 0.07 µg/mL) were identified as potent inhibitors of T-cells proliferation, in comparison to the standard drug, prednisolone (IC50 = 3.51 ± 0.03 µg/mL). Compound 7 (IC50 = 6.18 ± 0.04 µg/mL) showed a good activity. In addition, substrate 1 (IC50 ≤ 1 µg/mL), and its metabolites 2 (IC50 = 4.1 ± 0.60 µg/mL), and 6 (IC50 = 6.8 ± 0.8 µg/mL) also showed a potent inhibition of pro-inflammatory cytokine (TNF-α) production, as compared to the standards drug, pentoxifilline (IC50 = 94.8 ± 2.1 µg/mL). Whereas compounds 3 (IC50 = 57.9 ± 7.6 µg/mL), and 5 (IC50 = 27.2 ± 6.8 µg/mL) showed a moderate inhibition of TNF-α production, while compounds 4 and 7 showed no inhibition. Compounds 1-7 were found to be non-cytotoxic to 3T3 normal cell line (mouse fibroblast).
Assuntos
Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anticoncepcionais/metabolismo , Anticoncepcionais/farmacologia , Cunninghamella/metabolismo , Desogestrel/metabolismo , Desogestrel/farmacologia , Anti-Inflamatórios/química , Biotransformação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Anticoncepcionais/química , Desogestrel/química , Humanos , Relação Estrutura-Atividade , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacosRESUMO
Os fungos desempenham vários papéis que impactam a humanidade de diversas maneiras. Suas características metabólicas são importantes na biotecnologia, porém, tais microrganismos podem desencadear alguns problemas de saúde pública e até mesmo serem letais. Objetivo: detectar a presença de fungos no acervo de uma biblioteca no município de São José do Rio Preto. Metodologia: foram coletadas quarenta amostras nas superfícies inanimadas (livros, estantes, documentos, mapas, artigos e revistas) das principais salas da biblioteca com o auxílio de swabs umedecidos em solução salina estéril, posteriormente encaminhados ao laboratório de Biomedicina da Universidade Paulista UNIP. As amostras foram semeadas em meio de cultura ágar Sabouraud Dextrose (SDA), tendo adicionado cloranfenicol e incubadas a 30 °C. Foi realizada a colônia gigante em todas as cepas crescidas em SDA para a realização da técnica de microcultivo para a identificação dos fungos, de acordo com o Manual de Detecção e Identificação dos Fungos de Importância Médica da Agência Nacional de Vigilância Sanitária. Resultados: Houve positividade em trinta e uma amostras (78%) e em quatro delas foi observado mais de um tipo de colônia (13%). Das vinte e duas superfícies de livros analisadas, foram isolados e identificados: Aspergillus flavus, Aspergillus niger, Cunninghamella sp., Cladosporium sp., Curvularia sp., Mucor sp. e Nigrospora sp. Nas oito superfícies de estantes: Aspergillus flavus, Aspergillus niger, Aspergillus versicolor, Penicillium sp. e Scopulariopsis sp. e, nos dez documentos: Aspergillus nidulans, Aspergillus sp., Cladosporium sp., Cunninghamella sp. e Trichoderma sp. Conclusão: Os fungos encontrados estão amplamente distribuídos no ambiente como solo e ar e, por diversos fatores, instalam-se em locais como bibliotecas. Em condições favoráveis, podem infectar o homem e causar perdas patrimoniais para os acervos.
Fungi play many roles that impact humankind in different ways. Their metabolic characteristics are important in biotechnology; however, these microorganisms can trigger some public health problems or may even be lethal. Objective: detect the presence of fungi in the collection of a public library in the city of São José do Rio Preto, Brazil. Methods: a total of forty samples were collected from inanimate surfaces (books, shelves, documents, maps, articles and magazines) located in the main rooms of the library with swabs soaked in sterile saline solution and sent to the Universidade Paulista UNIP laboratories. The samples were plated in Sabouraud Dextrose Agar (SDA) supplemented with chloramphenicol and incubated at 30 °C. The colonies that grew in SDA were isolated in Potato Dextrose Agar for performing the slide culture technique for the identification of the fungi, performed according to the Manual of Detection and Identification of Fungi of Medical Importance from the Brazilian Health Surveillance Agency (ANVISA). Results: Thirty-one samples (78%) were positive, and in four of them more than one fungus genus was observed (13%). From the twenty-two book surfaces analyzed, the following fungi were isolated and identified: Aspergillus flavus, Aspergillus niger, Cunninghamella sp., Cladosporium sp., Curvularia sp., Mucor sp. and Nigrospora sp. On the eight shelves: Aspergillus flavus, Aspergillus niger, Aspergillus versicolor, Penicillium sp. and Scopulariopsis sp. The ten documents analyzed presented the following fungi: Aspergillus nidulans, Aspergillus sp., Cladosporium sp., Cunninghamella sp. and Trichoderma sp.. Conclusion: These fungi are widely distributed in the environment such as in the soil and air, and due to several factors, they colonize public places, such as libraries. In favorable conditions, they may infect humans and cause diseases.
Assuntos
Monitoramento Ambiental , Acervo de Biblioteca , Fungos , Penicillium , Aspergillus flavus , Aspergillus nidulans , Aspergillus niger , Trichoderma , Biotecnologia , Cladosporium , Cunninghamella , Ágar , InfecçõesRESUMO
Biotransformation of ent-kaur-16-en-19-oic acid using fungus Cunninghamella echinulata resulted in two novel hydroxylated metabolites together with five known compounds. Their structures were elucidated by means of extensive NMR and HR-ESI-MS data analysis. The eight compounds were measured for their cytotoxicity against the human breast carcinoma (MCF-7) and human hepatoblastoma (HepG-2) cell lines. Seven compounds showed no cytotoxicity to the two cell lines. One compound displayed moderate cytotoxicity against HepG-2 and MCF-7 with the IC50 values of 12.6 and 27.1â µM, respectively.
Assuntos
Cunninghamella/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cunninghamella/química , Diterpenos/química , Diterpenos/metabolismo , Células Hep G2 , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Conformação Molecular , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
BACKGROUND: The strategic development of therapeutic agents, capable of being targeted at their active sites, has been a major goal in treatment of cancer. The delivery of drugs for tumors has as its main challenge the development of safe and effective drugs, since the goal of chemotherapy is to eliminate the tumor completely without affecting healthy cells. The aim of present study was to investigate the antioxidant, anticancer activities of zidovudine and its α-O-glycosylated derivative obtained by biosynthesis of a filamentous fungi, Cunninghamela echinulata. METHODS: An evaluation of the cytotoxic potential of zidovudine and its α-O-glycosylated was performed in fibroblasts and melanoma cells by the tetrazolium reduction method (MTT) and the antioxidant activity of this derivative was observed. RESULTS: The antioxidant activity of zidovudine demonstrated an electrochemical oxidation potential of 0.91V, while the α-O-glycosylated derivative did not exhibit any antioxidant activity. The zidovudine exhibited low cytotoxicity for melanoma and fibroblast cells, while the α-O-glycosylated derivative presented better cytotoxicity on melanoma cells at a concentration of 10mg. mL-1. CONCLUSION: This study demonstrates the specific cytotoxicity of the glycoconjugate and suggests that glycosylation by biosynthesis can be a useful strategy for obtaining new anticancer compounds.
Assuntos
Antineoplásicos/farmacologia , Cunninghamella/metabolismo , Zidovudina/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosilação , Camundongos , Estrutura Molecular , Oxirredução , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Zidovudina/química , Zidovudina/metabolismoRESUMO
Cunninghamella species are aggressive, opportunistic fungi that are becoming more commonly reported in immunocompromised patients. We present a case of disseminated Cunninghamella sp. infection after stem cell transplant for refractory multiple myeloma with formation of bilateral pleural effusions and an aortic mycetoma. PCR analysis of the patient's aortic mycetoma demonstrated a 90% match to Cunninghamella spp. This case illustrates the potential for severe opportunistic fungal infections in immunocompromised patients that can mimic other disease processes and result in an accelerated demise.
Assuntos
Cunninghamella , Micetoma , Humanos , Hospedeiro Imunocomprometido , Mucormicose , Micetoma/diagnóstico , Infecções OportunistasRESUMO
BACKGROUND: Acute invasive fungal infections of the head and neck secondary to tyrosine kinase inhibitors are rare and potentially life-threatening events. CASE PRESENTATION: We report a case of mucormycosis of the thyroid gland in a patient known for chronic lymphocytic leukemia receiving ibrutinib who presented with a rapidly growing thyroid nodule and dysphonia. An acute invasive fungal infection was identified on a core needle biopsy; mucormycosis was confirmed on culture. The patient was successfully treated with surgical debridement and long-term antifungal therapy. CONCLUSION: Patients on ibrutinib may be at risk of acute invasive fungal infections of the head and neck.
Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Mucormicose/etiologia , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Nódulo da Glândula Tireoide/etiologia , Adenina/análogos & derivados , Idoso , Cunninghamella/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B/complicações , Masculino , Piperidinas , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Nódulo da Glândula Tireoide/microbiologia , Nódulo da Glândula Tireoide/patologiaRESUMO
A 49-year-old man underwent ABO-incompatible kidney transplantation with a living donor. At day 33 post-transplantation, he presented with undiagnosed epilepsy with generalized tonic-clonic seizures. At day 44 post-transplantation, he developed left-sided pneumonia attributed to Aspergillus fumigatus and treatment with liposomal amphotericin B was initiated. At day 51 post-transplantation, necrotic skin lesions appeared. DNA sequencing in a fresh cutaneous biopsy finally identified Cunninghamella Spp., a member of the order Mucorales. Unfortunately, the necrotic lesions spread, and the patient died at day 60 post-transplantation. This case report highlights the infectious risk related to ABO-incompatible kidney transplantation and suggests a requirement for rapid identification of every skin lesion, even in the early phases of immunosuppression.