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The need for new antimicrobial agents has become important in the last decade due to emerging resistance to a number of conventional antimicrobial agents. New approaches and sources are needed to generate novel and effective antimicrobials. For example, synergistic combinations between two or more agents may lead to new antimicrobial therapies. Furthermore, the increase in health problems caused by the exposure to agricultural crop pesticides and synthetic fungicides and the emerging development of organic farming has increased the necessity to develop natural products than can be used safely in controlling crop diseases. In this work, I present the first studies on the bioactive properties, particularly fungicidal activities, of mixtures of SRE and rhamnolipids. The in vitro results clearly showed strong synergism between SRE and rhamnolipids against phytopathogenic fungi and yeast. However, no activity was observed against bacteria. The hemolytic activities and cytotoxicities of SRE and SYRA were dose dependent. SRE acts on yeast and plant plasma membranes to cause numerous cellular effects. The effects are consistent with SRE's ability to form ion-conducting voltage sensitive channels in membrane bilayers. In addition, studies with yeast have revealed that sphingolipids and sterols modulate the fungicidal activity of SRE. Saccharomyces cerevisiae sphingolipid and sterol biosynthetic mutants were used to investigate the mechanism of action of SYRA against fungi. These results suggest that similar to SRE, SYRA antifungal action is promoted by sphingolipids and sterols of the plasma membrane and involves pore formation. I further explored the antimicrobial spectrum of syringopeptin SP25A and show that it specifically inhibits Gram-positive bacteria and yeast. I also investigated its mechanism of action against yeast and bacteria. The results revealed the role for D-alanylation of teichoic acids in modulating the susceptibility of B. subtilis to SP25A and other syringopeptins. This is consistent with the charged nature of the cyclic peptide portions of the syringopeptins, and it provides an explanation for SP25A's higher degree of specificity for Gram-positive bacteria. In addition and similar to SRE, SP25A antifungal action is promoted by sphingolipids and sterols of the plasma membrane and involves pore formation. Overall, the research shows that SRE and rhamnolipids are synergistically active against yeast and fungi and that the syringopeptins have antimicrobial activities against yeast and Gram-positive bacteria. Insights into the mechanisms of action of the SRE and rhamnolipid mixtures and the syringopeptins and their potential as novel antimicrobial agents are revealed.

The roam objectives of this PhD project were to relate anal~ te solubility in supercritical carbon dioxide via molecular structure and also to investigate the factors that influence the solubility and extraction of analytes in a supercritical fluid extraction (SFE) when using carbon dioxide as the solvent. The polarity of an analyte was selected as the key parameter to developing a means of estimating steroid solubility in supercritical carbon dioxide. Polarity can be estimated by the hydrophobicity term, log P (based on partition coefficients), and also of the solubility parameter, 0,. The use of partition coefficient in conjunction with a calculated solubility parameter was demonstrated as a reasonable means of estimating steroid solubility in supercritical carbon dioxide. Experimental determination of the solubility of several steroid compounds with a range in polarities in supercritical carbon dioxide was carried out in order to correlate solute polarity to the solute solubility. A chromatographic method was also investigated based on capacity factor measurements for the prediction of steroid solubility in supercritical carbon dioxide. The application of supercritical fluid extraction (SFE) \\<ith carbon dioxide and modified carbon dioxide for the extraction of four antifungals from an animal feed matrix has been investigated. The SFE experiments were designed to optimize e:\.1:raction conditions for the extraction of the antifungals from the animal feed to allow for the evaluation of the most significant variables influencing extraction. A method was also developed for the analysis of the SFE animal feed extracts by packed-column supercritical fluid chromatography. The modification of the mobile phase with polar modifier was necessary to elute the antifungals. The procedure provided an alternative separation selectivity to the existing reversed phase high performance liquid chromatography techniques with much shorter analysis time.

Orientador: Ana Claudia Pavarina / Resumo: O objetivo do estudo foi avaliar a eficácia da terapia fotodinâmica antimicrobiana (aPDT) associada a Nistatina (NYS) no tratamento de candidose oral induzida em camundongos infectados com Candida albicans resistente a fluconazol. Foram utilizados 174 camundongos Swiss fêmeas com aproximadamente 5 semanas de vida. Os animais foram imunossuprimidos com predinisolona 100 mg/kg no 1º, 5º e 13 º dias de experimento. No 2º dia, os animais foram sedados com 0,1 mL de cloridrato de clorpromazina e uma suspensão de C. albicans 107 UFC/mL foi inoculada na língua dos mesmos. Do dia 7 ao 11 os tratamentos foram realizados. No grupo aPDT foi utilizado 200 mg/L de Photodithazine (PDZ) associado à luz LED de 50 J/cm2 (grupo P+L+); no grupo (P+L-) foi utilizado apenas com PDZ; o grupo (P-L+) recebeu só luz LED e nos animais do grupo NYS o medicamento foi aplicado uma vez ao dia. Além disso, foi avaliada a combinação de duas terapias: P+L+NYS e NYS+P+L+. Um grupo recebeu apenas inoculação de C. albicans (grupo P-L-) e outro grupo de animais saudáveis (grupo CNI). Após os tratamentos, foi realizada a recuperação de C. albicans por meio de swabs estéreis. Então diluições seriadas foram realizadas e plaqueadas em placas de Petri com SDA. Após 48 horas de incubação a 37o C as colônias foram quantificadas e o número de UFC/mL foi determinado. Os camundongos foram sacrificados 24 horas e 7 dias após os tratamentos. Os resultados demonstraram que a combinação das terapias promoveu redução de 2,6 lo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of the present study was to evaluate of PDZ-mediated aPDT, as well as the association of this approach with antifungal nystatin, would be effective to treat oral candidosis in mice infected with fluconazole resistant C. albicans. Were used 174 female Swiss mice of 5 weeks-old-age approximately. The animals were immunosuppressed with predinisolone 100 mg/kg on the 1st, 5th and 13th days of the experiment. On day 2, the animals were sedated with 0.1 mL of chlorpromazine hydrochloride and a suspension of C. albicans 107 CFU/mL was inoculated into the tongue. From 7 to 11 the treatments were performed. In the aPDT group, was used 200 mg/L of Photodithazine (PDZ) associated with 50 J /cm2 LED light (P+L+ group). In the (P+L-) group was used only with PDZ; the group (P-L+) received only LED light and in the animals of the NYS group the drug was applied once a day. In addition, we evaluated the combination of two therapies: P+L+NYS and NYS+P+L+. One group received only inoculation of C. albicans (P-L- group) and another group of healthy animals (CNI group). After the treatments, recovery of C. albicans was performed by sterile swabs, then serial dilutions were performed and plated on Petri dishes with SDA. After 48 hours incubation at 37 °C the colonies were quantified, and the number of CFU/mL was determined. Mice were sacrificed 24 hours and 7 days after the treatments. The results showed that the combination of the therapies promoted reduction of 2.6 log10 and 2.1 log10 f... (Complete abstract click electronic access below) / Mestre

Malgré l’arsenal antifongique existant aujourd’hui, les mycoses superficielles sont en constante progression de par le monde et notamment dans le bassin caribéen. Nous nous sommes focalisés sur les pathologies qui posent, en Guadeloupe, de nombreux problèmes de résistance ou de rechute vis-à-vis des antifongiques actuels, à savoir : les dermatophyties, le Pityriasis versicolor (Malassezia sp.), les candidoses et les scytalidioses. Suite à ce constat, nous nous sommes tournés vers la flore guadeloupéenne où ont été sélectionnées dix plantes sur des critères ethnobotaniques, chimiotaxonomiques ou encore d’observations naturalistes avec un double objectif : trouver de nouveaux extraits antifongiques d’une part et, d’autre part, étudier leur composition et vérifier leur innocuité. Le screening antifongique in vitro des extraits c-hexane, EtOH et EtOH/eau (1:1, v/v) a été réalisé vis-à-vis de 4 dermatophytes, 1 Malassezia sp., 5 Candida spp. et 1 Scytalidium sp. Les extraits ont également été testés vis-à-vis d’un autre pathogène, Pneumocystis jirovecii responsable de la pneumocystose pulmonaire. Quatre plantes : Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum et Pluchea carolinensis ont été retenues afin de définir leurs cytotoxicités puis de procéder à l’isolement des composés responsables de leur activité antifongique par bioguidage. Cedrela odorata a montré une activité significative vis-à-vis de Pneumocystis jirovecii due en partie à la (+)-catéchine. Concernant les mycoses superficielles, Bursera simaruba et Cedrela odorata présentent une activité due à une synergie de composés non identifiés par bioguidage alors que Pluchea carolinensis et Enterolobium cyclocarpum doivent respectivement leurs activités à des flavonoïdes sulfatés et à des saponosides triterpéniques. Faisant suite à cette étude phytochimique et pharmacologique, la formulation des extraits sous forme de gels et vernis a été développée. Ainsi, cette étude permet d’apporter une réponse originale et efficace aux pathologies ciblées. / Despite the existing arsenal of antifungals today, superficial fungal infections have increased over the world and especially in the Caribbean basin. We focused our work on diseases that pose, in Guadeloupe, many problems of resistance or recurence towards current antifungals : dermatophytosis, Pityriasis versicolor (Malassezia sp.), Candidosis and Scytalidiosis. Following this observation, we were interested in the flora of Guadeloupe where ten plants were selected on natural observation, ethnobotanical or chemotaxonomical criteria with a dual purpose: to find new antifungal extracts on the one hand, and secondly, to study their composition and verify their safety. The in vitro screening of c-hexane, EtOH and EtOH/water (1:1, v/v) extracts, was made towards four dermatophytes, one Malassezia sp., five Candida spp. and one Scytalidium sp. The extracts were also tested on another pathogen, Pneumocystis jirovecii which is responsible of pneumonia. Four plants: Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis were chosen to define their cytotoxicities and then we proceed to the isolation of active compounds by bioguiding. Cedrela odorata showed significant activity on Pneumocystis jirovecii and (+)-catechin was found to be partly responsible of this activity. Concerning the research on the superficial mycoses, Bursera simaruba and Cedrela odorata’s activities were due to a synergy of compounds unidentified by bioguiding while Pluchea carolinensis and Enterolobium cyclocarpum owe their activities to sulfated flavonoids and triterpene saponins, respectively. Following to these phytochemical and pharmacological studies, the drug formulation of the extracts has been developed. Thus, this study could be an original and effective response to the targeted disease.

Fungal infections have a significant impact on the world population, with estimates of over 1.6 million deaths a year. One contributing factor is the increasing number of fungi resistant to the current clinical treatments, including the last approved family of antifungal compounds introduced into the market over a decade ago. This is driving the search for new antifungals with different biological targets. A new potential antifungal occidiofungin, is a cyclic glycolipopeptide isolated from the soil bacterium Burkholderia contaminans MS14 with a broad spectrum of activity against both human and plant pathogens. Kill kinetics demonstrated that this compound is fungicidal and activates the cell wall integrity pathway at suboptimal dosing as determined by Mkc1 MAPK phosphorylation studies. As three of the four classes of currently available antifungals target ergosterol or ergosterol biosynthesis, the bioactivity of occidiofungin was assayed in the presence of ergosterol containing DOPC vesicles and was shown to retain antifungal properties. Occidiofungin was also found to have a similar activity profile against the S. cerevisiae -1,3-glucan synthesis mutant, indicating that it does not share a target with the fourth class of antifungals. Stability testing showed occidiofungin retained in vitro potency in the presence of human serum, across a broad range of pH and temperature conditions, and was resistant to gastric proteases. Based on cell morphology, occidiofungin did not target a specific stage of the yeast cell cycle, however cells were smaller in size and acquired ‘dancing bodies’, both properties of apoptosis. This was confirmed with data showing concentration dependent increases in DNA fragmentation, reactive oxygen species, and extracellular localization of phosphatidylserine. In addition to these findings, cells deleted for the yeast caspase gene exhibit a 2old resistance to occidiofungin. While SEM showed no morphological differences between treated and untreated cells, TEM did identify a thinning of the cell wall and inclusion bodies in cells treated with occidiofungin. As a stable fungicidal compound that induces apoptosis in yeast, occidiofungin has a great potential to become a new candidate drug for clinical use in treating fungal infections, including those resistant to current antifungals.

Onicomicose é uma infecção crônica das unhas provocadas por fungos. É a doença mais comum das unhas em todo o mundo e constitui cerca de metade de todas as alterações ungueais em indivíduos imunocompetentes e imunossuprimidos. Nos últimos anos, vários estudos tem demonstrado aumento na prevalência de onicomicose. Esse aumento pode ser atribuído a diversos fatores, incluindo o aumento da expectativa de vida, e propagação do vírus da imunodeficiência humana (HIV). Nesse sentido, o número de pacientes renais crônicos vem aumentando em todo mundo. No entanto, a literatura relata poucos estudos sobre a prevalência e as características das onicomicoses nestes pacientes. Diante disso, nossos objetivos foram determinar a prevalência, etiologia e perfil de suscetibilidade das onicomicoses provenientes de pododáctilos de pacientes dialíticos (DL), receptores de transplante renal (RTR) e pacientes grupo controle. Foram examinados 510 pacientes, sendo 336 provenientes da Unidade de Transplante Renal (149 DL e 187 RTR), e 174 pacientes do Ambulatório de Clínica Geral, sem histórico de doença associada à imunossupressão (Grupo controle). Os isolados foram identificados por testes fenotípicos e moleculares. O perfil de suscetibilidade foi realizado pelo método de microdiluição em caldo frente aos fármacos fluconazol, itraconazol, voriconazol e terbinafina. A prevalência de onicomicose foi de 23,4% nos pacientes DL e 23,0% nos RTR, significativamente maior que no grupo controle (13,2%). Nos pacientes DL, onicomicose foi associada com diabetes, mas não com o tempo de diálise e sexo. Nos pacientes RTR, onicomicose foi mais prevalente em homens, mas não houve associação com duração do transplante, diabetes e protocolo de tratamento imunossupressor. Trichophyton rubrum foi a agente mais prevalente (45,9%), seguido por T. mentagrophytes (24,5%) e Candida parapsilosis (18%). Todos antifúngicos foram eficazes frente aos isolados de dermatófitos, sendo terbinafina o mais eficiente. Os isolados de C. parapsilosis foram todos sensíveis aos quatro antifúngicos de acordo com os atuais \"end-points\". Nossos achados permitiram concluir que pacientes renais (DL e RTR) tem risco aumentado de desenvolver onicomicose. Nossos dados também revelaram que a etiologia e a suscetibilidade das espécies isoladas são comparáveis aos encontrados em outros grupos de pacientes não renais descritos na literatura. / Onychomycosis is a chronic fungal infection of the nail. It is the most common disorder of nails worldwide and constitutes about 50% of all nail changes of the immunosuppressed and healthy patients. In recent years, several reports have shown increased prevalence of onychomycosis. This increase can be attributed to several factors, including increased life expectancy, and to the human immunodeficiency virus (HIV) epidemics. In this regard, the number of chronic renal patients is also increasing worldwide. However, the literature reports few studies on onychomycosis in these patients. Therefore, our objectives were to determine the prevalence, etiology and susceptibility profile of onychomycosis of the toenail of patients undergoing hemodialysis treatment (HD), kidney transplant recipients (KTR) and control patients. Were examined 510 patients, 336 attending the Renal Transplantation Unit (187 KTR e 149 HD) and 174 patients attending an internal medicine outpatient service with diseases other than renal disease (control group). The isolates were identified by phenotypic and molecular tests. Antifungal susceptibility tests were performed using a broth microdilution method against the antifungal drugs voriconazole, itraconazole, fluconazole and terbinafine. The prevalence of onychomycosis in HD patients (23.4%) and KTR (23.0%) was significantly higher than control group (13.2%). In HD patients, onychomycosis was associated with diabetes but not duration of dialysis and gender. In KTR, onychomycosis was more prevalent in males, but not associated with duration of transplantation, diabetes or immunosuppressive protocols. Trichophyton rubrum was the most prevalent species (45.9%) followed by T. mentagrophytes (24.5%) and Candida parapsilosis (18%). While all antifungals were efficient against the dermatophyte isolates, terbinafine was the most effective. All C. parapsilosis isolates were sensitive to the antifungals according to the current end-points. In conclusion, this study shows that HD patients and KTR are at high risk of contracting onychomycosis. Our data also show that the etiology and susceptibility of the species are comparable with those found in other groups of non-renal patients described in the literature.

O presente trabalho teve como objetivo realizar a extração de lignanas e outros compostos fenólicos do farelo de linhaça desengordurado e avaliar a atividade antifúngica dessas frações frente a fungos leveduriformes do gênero Candida. Obteve-se o extrato bruto através de maceração com solução hidroalcólica. O extrato bruto foi hidrolisado em condições básicas e ácidas, objetivando-se o isolamento de heterosídeos e agliconas, respecitvamete. A lignana secoisolariciresinol diglicosídeo foi quantificada por cromatografia líquida de alta eficiência. O flavonoide herbacetin diglicosídeo e a lignana anidrosecoisolariciresinol foram identificados por espectrometria de massas. A avaliação da atividade antifúngica foi realizada in vitro e foi observado que tanto o extrato bruto como o extrato obtido por hidrólise alcalina inibiram o desenvolvimento de Candida krusei CK 02 e Candida parapsilosis RL 20 na concentração de 500 μg/mL. O extrato obtido por hidrólise ácida, na mesma concentração, apresentou atividade inibitória frente a Candida krusei CK 02, Candida parapsilosis RL 20 e Candida tropicallis ATCC 750. A investigação das condições de hidrólise ácida, a melhor caracterização de seus componentes e a avaliação da ação antifúngica dos extratos frente a outros gêneros de fungos constituem perspectivas para trabalhos futuros. / The aim of the present work was carry out the extraction of lignans and other phenolic compounds from defatted flaxseed meal and evaluate the antifungal activity of these fractions against yeast fungi of Candida genus. The crude extract was obtained by maceration with a hydroalcoholic solution. The crude extract was hydrolyzed in basic and acidic conditions, aiming the isolation of glycosides and aglycones, respectively. Secoisolariciresinol diglucoside was quantified by highperformance liquid chromatography. The flavonoid herbacetin diglucoside and the lignan anhydrosecoisolariciresinol were identified by mass spectrometry. The avaliation of antifungal activity was performed in vitro and it was observed that both the crude extract and the extract obtained by alkaline hydrolysis inhibited the development of Candida krusei CK 02 and Candida parapsilosis RL 20 at a concentration of 500 ug/mL. The extract obtained by acid hydrolysis, in the same concentration, showed inhibitory activity against Candida krusei CK 02, Candida parapsilosis RL 20 and Candida tropicallis ATCC 750. The investigation of acid hydrolysis conditions, a better characterization of its components and the avaliation of antifungal activity against other fungi genera represents good potencial for future work.

nÃo hà / O aumento nos Ãltimos anos de indivÃduos imunocomprometidos, como portadores da SÃndrome da ImunodeficiÃncia Adquirida, de doenÃas malignas, transplantados e outros usuÃrios de terapias imunossupressoras, favorece o surgimento de infecÃÃes oportunistas, principalmente as de teor fÃngico, como a candidÃase e a criptococose. Apesar de a terapia antifÃngica atual ser eficiente na maioria dos casos, algumas vezes fazem-se necessÃrias novas drogas que atuem como alternativa ou como coadjuvantes no tratamento para potencializar o efeito dos antifÃngicos utilizados. As estatinas sÃo fÃrmacos hipolipemiantes mais prescritos mundialmente para doenÃas cardiovasculares. Entretanto, recentemente, tem sido descritos outros efeitos benÃficos destas drogas, como, por exemplo, o controle de infecÃÃes. Este trabalho teve como objetivo determinar a atividade antifÃngica in vitro das estatinas ante 51 cepas de Candida, sendo 16 de C. albicans, 11 de C. krusei, 12 de C. tropicalis e 12 de C. parapsilosis, e 25 cepas de Cryptococcus, sendo 12 de C. gattii e 13 de C. neoformans, por meio de testes de microdiluiÃÃo em caldo, segundo documento M27-A3 padronizado pelo CLSI. O intervalo de concentraÃÃo testado para pravastatina foi de 50 a 0,0977 mg/mL, para sinvastatina, 1 a 0,0020 mg/mL e para atorvastatina, 10 a 0,0200 mg/mL. Pravastatina inibiu 37 leveduras do gÃnero Candida apresentando concentraÃÃo inibitÃria mÃnima (CIM) na faixa de 1,56 a 6,25 mg /mL e as cepas restantes nÃo foram inibidas mesmo na maior concentraÃÃo testada (50 mg /mL), enquanto que sinvastatina e atorvastatina apresentaram atividade antifÃngica sobre todas as 51 cepas avaliadas, apresentando CIMs de 0,02 a 1 mg / mL e 0,04 a 5,00 mg / mL, respectivamente. Para o gÃnero Cryptococcus, apenas 4 cepas foram inibidas ante a pravastatina (CIM = 25 mg / mL), por outro lado, sinvastatina inibiu todas as 25 cepas (CIM = 0,06 a 1 mg / mL), e atorvastatina apenas 8 cepas (CIM = 0,62 a 2,5 mg / mL), sendo que as 17 restantes nÃo foram inibidas mesmo na maior concentraÃÃo testada ( &#8805; 10 mg / mL). Foi determinada concentraÃÃo fungicida mÃnima (CFM) de pravastatina sobre 15 cepas do gÃnero Candida (CFM = 3,12 a 25 mg / mL), de sinvastatina sobre 34 cepas (CFM = 0,03 a 1 mg / mL), e de atorvastatina sobre 16 cepas (CFM = 0,04 a 0,31 mg / mL). Para o gÃnero Cryptococcus, das 25 cepas testadas, pravastatina exibiu CFM sobre apenas 3 cepas (CFM = 50 mg / mL), sinvastatina sobre 21 cepas (CFM = 0,12 a 1 mg / mL), e atorvastatina sobre 1 cepa (CFM = 1 mg / mL). Esta atividade inibitÃria in vitro de estatinas sobre espÃcies de Candida e Cryptococcus, abre uma perspectiva importante para a investigaÃÃo do possÃvel uso destas drogas com finalidade antifÃngica in vivo. / In the past years, fungal opportunistic infections, especially, candidiasis and cryptococcosis, have become more frequent because of the increase in the number of immunocompromised individuals, such as AIDS, transplant and cancer patients and those that are on immunosuppressive therapy. In spite of being effective, sometimes it is necessary to use new drugs as alternatives or as adjuvants in order to potentiate the effect of the classical antifungal therapy. Statins are the most prescribed hypolipemiant drugs worldwide for preventing cardiovascular diseases. However, other benefic effects for these drugs have been described, such as the control of infections. This work aimed at determining the antifungal activity of statins against Candida spp. and Cryptococcus spp. The minimum inhibitory concentrations (MICs) for three different statins (pravastatin, simvastatin and atorvastatin) were determined against 51 strains of Candida spp. (16 C. albicans, 11 C.krusei, 12 C. tropicalis and 12 C. parapsilosis) and 25 strains of Cryptococcus spp. (12 C. gattii and 13 C. neoformans), through broth microdilution assay, according to the Clinical Laboratory Standards Institute (CLSI - Document M27-A3). The concentration tested for pravastatin ranged from 50 to 0.0977 mg/mL, for simvastatin, it ranged from 1 to 0.0020 mg/mL and, for atorvastatin, it varied from 10 to 0.0200 mg/mL. Pravastatin inhibited 37 Candida strains, with MICs varying from 1.56 to 6.25 mg/mL and the remaining strains were not inhibited, even at the highest concentration tested (50 mg/mL). Simvastatin and atorvastatin, on the other hand, inhibited all 51 Candida strains evaluated, presenting MICs ranging from 0.02 to 1 mg/mL and from 0.04 to 5 mg/mL, respectively. Concerning Cryptococcus spp., only four strains were inhibited by pravastatin (MIC=25 mg/mL), while all 25 strains were inhibited by simvastatin (0.06&#8804;MIC&#8804;1 mg/mL) and eight were inhibited by atorvastatin (0.62&#8804;MIC&#8804;2.5 mg/mL) and the remaining 17 were not susceptible to the highest atorvastatin concentration tested (10 mg/mL). The minimum fungicidal concentrations (MFCs) for the tested statins were also determined. The MFC for pravastatin against Candida spp. was determined against 15 strains (3.12&#8804;MIC&#8804;25 mg/mL). The MFC values for simvastatin were determined for 34 strains of Candida spp. (0.03&#8804;MFC&#8804;1 mg/mL), while those for atorvastatin were determined against 16 strains (0.04&#8804;MFC&#8804;0,31 mg/mL). Concerning Cryptococcus spp., the 25 strains tested, MFC values for pravastatin were found against three strains (MFC=50 mg/mL), while those for simvastatin were determined against 21 strains (0.12&#8804;MFC&#8804;1 mg/mL) and those for atorvastatin were determined against one single strain (MFC=1 mg/mL). This in vitro inhibitory activity of statins against Candida spp. and Cryptococcus spp. creates an important perspective for the use of these drugs in vivo in order to control fungal infections.

O presente trabalho teve como objetivo realizar a extração de lignanas e outros compostos fenólicos do farelo de linhaça desengordurado e avaliar a atividade antifúngica dessas frações frente a fungos leveduriformes do gênero Candida. Obteve-se o extrato bruto através de maceração com solução hidroalcólica. O extrato bruto foi hidrolisado em condições básicas e ácidas, objetivando-se o isolamento de heterosídeos e agliconas, respecitvamete. A lignana secoisolariciresinol diglicosídeo foi quantificada por cromatografia líquida de alta eficiência. O flavonoide herbacetin diglicosídeo e a lignana anidrosecoisolariciresinol foram identificados por espectrometria de massas. A avaliação da atividade antifúngica foi realizada in vitro e foi observado que tanto o extrato bruto como o extrato obtido por hidrólise alcalina inibiram o desenvolvimento de Candida krusei CK 02 e Candida parapsilosis RL 20 na concentração de 500 μg/mL. O extrato obtido por hidrólise ácida, na mesma concentração, apresentou atividade inibitória frente a Candida krusei CK 02, Candida parapsilosis RL 20 e Candida tropicallis ATCC 750. A investigação das condições de hidrólise ácida, a melhor caracterização de seus componentes e a avaliação da ação antifúngica dos extratos frente a outros gêneros de fungos constituem perspectivas para trabalhos futuros. / The aim of the present work was carry out the extraction of lignans and other phenolic compounds from defatted flaxseed meal and evaluate the antifungal activity of these fractions against yeast fungi of Candida genus. The crude extract was obtained by maceration with a hydroalcoholic solution. The crude extract was hydrolyzed in basic and acidic conditions, aiming the isolation of glycosides and aglycones, respectively. Secoisolariciresinol diglucoside was quantified by highperformance liquid chromatography. The flavonoid herbacetin diglucoside and the lignan anhydrosecoisolariciresinol were identified by mass spectrometry. The avaliation of antifungal activity was performed in vitro and it was observed that both the crude extract and the extract obtained by alkaline hydrolysis inhibited the development of Candida krusei CK 02 and Candida parapsilosis RL 20 at a concentration of 500 ug/mL. The extract obtained by acid hydrolysis, in the same concentration, showed inhibitory activity against Candida krusei CK 02, Candida parapsilosis RL 20 and Candida tropicallis ATCC 750. The investigation of acid hydrolysis conditions, a better characterization of its components and the avaliation of antifungal activity against other fungi genera represents good potencial for future work.