Antifúngicos naturais e sintéticos: estudo dos mecanismos de ação em sistema de infecção in vitro empregando cepas de Cryptococcus

A criptococose é uma micose sistêmica e oportunista causada principalmente pelas leveduras Cryptococcus neoformans e Cryptococcus gattii. Entre as principais manifestações clínicas estão o desenvolvimento de meningite, encefalite, meningoencefalite e infecções pulmonares. Estima-se que mais de um milhão dos casos de criptococose ocorrem por ano em indivíduos HIV positivos, o que classifica esta doença como a terceira mais importante entre as infecções fúngicas sistêmicas. A ecologia deste gênero está diretamente relacionada ao meio ambiente, sendo a espécie C. neoformans, comumente encontrada em excretas secas de pombos (Columbia livia) e a espécie C. gattii é encontrada, principalmente, em plantas, como espécies de Eucalyptos. O tratamento da criptococose é realizado com os fármacos antifúngicos, anfotericina B e fluconazol, sendo este último de ação fungistática utilizado para tratamento de longo prazo, que apesar de eficiente, pode causar uma série de reações adversas e ainda desenvolvimento de resistência. Tendo em vista o difícil controle da levedura e o tratamento, este trabalho tem como objetivo principal, a pesquisa de substâncias naturais com alto potencial antifúngico com finalidade saneante e medicamentosa, combatendo a levedura em seu nicho ecológico natural e também atuando no combate à infecção no hospedeiro. Uma forma de diminuir os casos desta infecção é através do processo de desinfecção ambiental com produtos saneantes, os quais apresentam capacidade fungicida. Por meio do projeto Biota/FAPESP, foram selecionados dois triterpenóides quinonamétideos extraídos de Maytenus ilicifolia, a maitenina e a pristimerina, as quais apresentaram potentes CIMs anti-Cryptococcus, mais de 90 % de eficiência na desinfecção e baixa toxicidade, o que revela que...Cryptococcosis is a systemic mycosis caused mainly by opportunistic yeast Cryptococcus neoformans and Cryptococcus gattii. Among the main clinical manifestations are the development of encephalitis, meningoencephalitis and pulmonar infections. It is estimated that more than one million cases of cryptococcosis occur per year in HIV positive individuals, which classifies the disease as the third among the most importante systemic fungal infections. The ecology of this genus is directly related to the environment. Specie C. neoformans is commonly found in dried excremento of pigeons (Columbia livia) and the species C. gattii is found primarily in plants such as Eucalyptus species. Cryptococcosis treatment is performed with the antifungal drugs amphotericin B and fluoconazole, the later being of a fungistatic used to treat long-term, while effective, may cause a number of adverse reactions and also the development of resistence. Given the difficult control of the yeast and treatment, this work has as main objective, the research of natural substances with high potential antifungal drug with purpose and saneante, fighting yeast in their natural ecological niche and also acting in fighting infection in the host. One way to reduce the cases of infection is through the capacity fungicide. Through the Project BIOTA / FAPESP, we selected two quinonametides triterpenids extracted from Maytenus ilicifolia, the maitenin and pristimerin, which showed potente anti-Cryptococcus MICs, more than 90 % of the disinfection efficiency and low toxicity... (Complete abstract click electronic access below)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Estudo sobre o conhecimento e uso popular da garra-do-diabo (harpagophytum procumbens) como planta medicinal

The plant Harpagophytum procumbens is native to the Kalahari Desert and Steppes of Namibia, it belongs to the Pedaliaceae family and is popularly known in Brazil as "diabo's claw". The anti-inflammatory properties attributed to this medicinal plant are given by the presence of the prevalent active compound harpagoside, which makes H. procumbens stand out as herbal medicine for the treatment of diseases such as arthritis, osteoarthritis and rheumatism. Despite not being originally from Brazil, the herbal medicine can be found in the National List of Essential Medicines of the SUS, in portuguese the initial letters (RENAME). The present work aims to evaluate the knowledge and acceptance of the population about the use of H. procumbens as herbal medicine for alternative and auxiliary treatment for inflammatory diseases as well as to warn about the indiscriminate use of herbal medicines. The data of this study were obtained through an online questionnaire which was answered by 300 volunteers, over 18 years old, who answered ten questions about herbal medicines and devil's claw. The results demonstrate the level of knowledge of the interviewees about H. procumbens and the acceptance in the use of herbal medicines obtained by this work. Such results contributed to scientific bases on the rational use of herbal medicines, especially the plant H. procumbens, on its anti- inflammatory effect. Also guiding the population on the safe use of herbal medicine, thus contributing to health promotion.A planta Harpagophytum procumbens é originária do deserto de Kalahari e Estepes da Namíbia perpertence à família Pedaliaceae e é conhecida popularmente no Brasil como “garra-do- diabo”. As propriedades anti-inflamatórias atribuídas à esta planta medicinal, são dadas pela presença do composto ativo prevalente o harpagosídeo, o que faz H. procumbens destacar-se como um fitoterápico para o tratamento de doenças como artrite, osteoartrite e reumatismo. Apesar de não ser originária do Brasil, pode-se encontrar o fitoterápico na Relação Nacional de Medicamentos Essenciais do SUS (RENAME). O presente trabalho tem como objetivo avaliar o conhecimento e aceitação da população sobre o uso de H. procumbens como fitoterápico para o tratamento alternativa e auxiliar para doenças inflamatórias assim como alertar sobre o uso indiscriminado de medicamentos fitoterápicos. Os dados deste estudo foram obtidos por meio de questionário online o qual foi respondido por 300 voluntários, maiores de 18 anos, os quais responderam dez perguntas sobre fitoterápicos e garra-do-diabo. Os resultados   demonstram   o   baixo   nível   de   conhecimento   dos entrevistados sobre o H. procumbens, no entanto, mostrou uma boa aceitação no uso de medicamentos fitoterápicos. Tais resultados, contribuiem para bases científicas sobre o uso racional de fitoterápicos, especialmente a planta H. procumbens, sobre seu efeito anti-inflamatório. Ainda orientando a população sobre o uso seguro de fitoterápico, contribuindo assim, para a promoção da saúde

Environmental isolation, biochemical identification, and antifungal drug susceptibility of Cryptococcus species

Introduction The incidence of opportunistic fungal infections has increased in recent years and is considered an important public health problem. Among systemic and opportunistic mycoses, cryptococcosis is distinguished by its clinical importance due to the increased risk of infection in individuals infected by human immunodeficiency virus. Methods To determine the occurrence of pathogenic Cryptococcus in pigeon excrement in the City of Araraquara, samples were collected from nine environments, including state and municipal schools, abandoned buildings, parks, and a hospital. The isolates were identified using classical tests, and susceptibility testing for the antifungal drugs (fluconazole, itraconazole, voriconazole, and amphotericin B) independently was also performed. After collection, the excrement samples were plated on Niger agar and incubated at room temperature. Results A total of 87 bird dropping samples were collected, and 66.6% were positive for the genus Cryptococcus. The following species were identified: Cryptococcus neoformans (17.2%), Cryptococcus gattii (5.2%), Cryptococcus ater (3.5%), Cryptococcus laurentti (1.7%), and Cryptococcus luteolus (1.7%). A total of 70.7% of the isolates were not identified to the species level and are referred to as Cryptococcus spp. throughout the manuscript. Conclusions Although none of the isolates demonstrated resistance to antifungal drugs, the identification of infested areas, the proper control of birds, and the disinfection of these environments are essential for the epidemiological control of cryptococcosis

Anti-Trichophyton Activity of Protocatechuates and Their Synergism with Fluconazole

Dermatophytosis and superficial mycosis are a major global public health problem that affects 20-25% of the world's population. The increase in fungal resistance to the commercially available antifungal agents, in conjunction with the limited spectrum of action of such drugs, emphasises the need to develop new antifungal agents. Natural products are attractive prototypes for antifungal agents due to their broad spectrum of biological activities. This study aimed to verify the antifungal activity of protocatechuic acid, 3,4-diacetoxybenzoic, and fourteen alkyl protocatechuates (3,4-dihydroxybenzoates) against Trichophyton rubrum and Trichophyton mentagrophytes and to further assess their activities when combined with fluconazole. Susceptibility and synergism assays were conducted as described in M38-A2 (CLSI), with modifications. Three strains of Trichophyton rubrum and three strains of Trichophyton mentagrophytes were used in this work. The pentyl, hexyl, heptyl, octyl, nonyl, and decyl protocatechuates showed great fungicidal effects, with minimum inhibitory concentration (MIC) values ranging from 0.97 to 7.8 mg/L. Heptyl showed a synergistic activity (FIC index = 0.49), reducing the MIC of fluconazole by fourfold. All substances tested were safe, especially the hexyl, heptyl, octyl, and nonyl compounds, all of which showed a high selectivity index, particularly in combination with fluconazole. These ester associations with fluconazole may represent a promising source of prototypes in the search for anti-Trichophyton therapeutic agents.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Preliminary evaluation of circulating microRNAs as potential biomarkers in paracoccidioidomycosis

Copyright © Spandidos Publications 2021. All rights reserved.MicroRNAs (miRNAs) are small RNAs (length, 19-24 nucleotides) that regulate gene expression by either mRNA degradation or translational inhibition of proteins. Circulating miRNAs, which are extremely stable and protected from RNAse-mediated degradation in body fluids, have appeared as candidate biomarkers for numerous diseases. However, little is known about circulating miRNAs in fungal infections. Paracoccidioidomycosis (PCM) is caused by the Paracoccidioides species, and is endemic in Central and South America, with predominance in adult male workers from rural areas. The current study aimed to identify a serum miRNA expression profile that could serve as a novel diagnostic biomarker for PCM. Total RNA was isolated and the levels of circulating miRNAs were compared between patients with PCM and healthy control subjects using reverse transcription-quantitative polymerase chain reaction. Bioinformatic analysis was used to evaluate the potential roles of these miRNAs in PCM. Eight miRNAs were differentially expressed in serum samples from patients with PCM. These miRNAs are associated with apoptosis and immune response. The identified miRNAs facilitate with understanding the regulatory mechanisms involved in the host-parasite interaction of PCM. Furthermore, considering that the diagnosis of PCM presents difficulties, these miRNAs may serve as novel biomarkers for this disease.The present study was supported by grants from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/Fundação para a Ciência e a Tecnologia (grant no. 345/13), the Conselho Nacional de Pesquisa e Desenvolvimento the Fundação de Amparo à Pesquisa do Estado de São Paulo (grant no. 2014/10446-9) and Programa de Apoio ao Desenvolvimento Científico da Faculdade de Ciências Farmacêuticas da UNESP.info:eu-repo/semantics/publishedVersio

Chemical and antifungal investigations of six Lippia species (Verbenaceae) from Brazil

The Lippia genus is used in ethnobotany as food, beverages, seasoning and antiseptic remedies, among others. The chemical compositions of fifteen extracts of six Lippia species were investigated comparatively by HPLC-PDA. To avoid data replication of previous works on this genus, Lippia lupulina Cham. root ethanol extract was selected for isolation procedures based on Principal Component Analyses (PCA) of such data. Seven compounds previously unreported in this genus were isolated from this extract (a triterpene, two furanonaphtoquinones, a furanochromone, an isoflavone, a stilbene and an iridoid). The activities of extracts, fractions and pure compounds towards Candida albicans, Candida krusei, Candida parapsilosis and Cryptococcus neoformans were investigated. Two fractions from the extract of Lippia salviaefolia leaves showed marked inhibition of fungal growth, in addition to verbascoside and asebogenin, which showed MICs lower than 15.6 mu g/ml and may be promising leads for the development of new antifungal agents, especially against C. neoformans. (C) 2012 Elsevier Ltd. All rights reserved

Synthesis, antifungal activity of caffeic acid derivative esters, and their synergism with fluconazole and nystatin against Candida spp

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOWe tested the antifungal potential of caffeic acid and 8 of its derivative esters against Candidaalbicans ATCC 90028 and 9 clinical isolatesand carried out a synergism assay with fluconazole and nystatin. Propyl caffeate (C3) showed the best antifungal activity against the tested strains. When in combination, C3 markedly reduced the MIC of fluconazole and nystatin with synergistic effect up to 64-fold. Finally, C3 showed a high IC50 value and selective indexagainst oral keratinocytes, demonstrating low toxicity against this cell type and selectivity for yeast cells. Further research should confirm its antifungal potential for development of combined therapy to treat C. albicans infections. (C) 2016 Elsevier Inc. All rights reserved.We tested the antifungal potential of caffeic acid and 8 of its derivative esters against Candidaalbicans ATCC 90028 and 9 clinical isolatesand carried out a synergism assay with fluconazole and nystatin. Propyl caffeate (C3) showed the best antifungal activity against the tested strains. When in combination, C3 markedly reduced the MIC of fluconazole and nystatin with synergistic effect up to 64-fold. Finally, C3 showed a high IC50 value and selective indexagainst oral keratinocytes, demonstrating low toxicity against this cell type and selectivity for yeast cells. Further research should confirm its antifungal potential for development of combined therapy to treat C. albicans infections864387391CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO474335/2013-