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[PMID]:29206032
[Au] Autor:Rajendran K; Anwar A; Khan NA; Siddiqui R
[Ad] Endereço:Department of Biological Sciences, School of Science and Technology, Sunway University , Bandar Sunway 47500, Malaysia.
[Ti] Título:Brain-Eating Amoebae: Silver Nanoparticle Conjugation Enhanced Efficacy of Anti-Amoebic Drugs against Naegleria fowleri.
[So] Source:ACS Chem Neurosci;8(12):2626-2630, 2017 12 20.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.
[Mh] Termos MeSH primário: Amebicidas/administração & dosagem
Nanopartículas Metálicas/administração & dosagem
Naegleria fowleri/efeitos dos fármacos
Naegleria fowleri/fisiologia
Nanoconjugados/administração & dosagem
Nanoconjugados/química
Prata/administração & dosagem
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Combinação de Medicamentos
Sinergismo Farmacológico
Fluconazol/administração & dosagem
Nanopartículas Metálicas/química
Nanopartículas Metálicas/ultraestrutura
Naegleria fowleri/citologia
Nanocápsulas/administração & dosagem
Nanocápsulas/química
Nanocápsulas/ultraestrutura
Nanoconjugados/ultraestrutura
Nistatina/administração & dosagem
Tamanho da Partícula
Prata/química
Taxa de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amebicides); 0 (Drug Combinations); 0 (Nanocapsules); 0 (Nanoconjugates); 1400-61-9 (Nystatin); 3M4G523W1G (Silver); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.7b00430


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[PMID]:28450174
[Au] Autor:Ribeiro NQ; Costa MC; Magalhães TFF; Carneiro HCS; Oliveira LV; Fontes ACL; Santos JRA; Ferreira GF; Araujo GRS; Alves V; Frases S; Paixão TA; de Resende Stoianoff MA; Santos DA
[Ad] Endereço:Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
[Ti] Título:Atorvastatin as a promising anticryptococcal agent.
[So] Source:Int J Antimicrob Agents;49(6):695-702, 2017 Jun.
[Is] ISSN:1872-7913
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cryptococcosis caused by Cryptococcus gattii leads to pneumonia and meningoencephalitis, and has a high mortality rate worldwide due to the inadequacy of available therapy and increasing drug resistance. There is a need to develop effective treatments, and drug repositioning is an interesting alternative to achieve new strategies to treat cryptococcosis. Atorvastatin (ATO), a statin currently used to treat hypercholesterolaemia, was tested in this study as an adjuvant to control infections caused by C. gattii. Several aspects of the effect of ATO on the host and the yeast were evaluated, with particular focus on the association of ATO with fluconazole (FLC), which (i) reduced ergosterol content in the cell membrane and altered properties of the polysaccharide capsule of C. gattii; (ii) increased the production of reactive oxygen species by macrophages; and (iii) reduced yeast phagocytosis and the intracellular proliferation rate. In an animal model, infected mice treated with ATO + FLC showed increased survival, improved clinical condition, and reduced fungal burden in the lungs and brain. This study is the first to perform in vivo tests with ATO + FLC for the treatment of cryptococcosis. The results suggest that ATO may be an important adjuvant for the treatment of cryptococcosis.
[Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico
Antifúngicos/uso terapêutico
Atorvastatina Cálcica/uso terapêutico
Criptococose/tratamento farmacológico
Cryptococcus gattii/efeitos dos fármacos
Reposicionamento de Medicamentos
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Antifúngicos/farmacologia
Atorvastatina Cálcica/farmacologia
Criptococose/microbiologia
Modelos Animais de Doenças
Quimioterapia Combinada/métodos
Fluconazol/farmacologia
Fluconazol/uso terapêutico
Masculino
Camundongos Endogâmicos C57BL
Análise de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Antifungal Agents); 48A5M73Z4Q (Atorvastatin Calcium); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29426303
[Au] Autor:Singh S; Shrivastav A; Agarwal M; Gandhi A; Mayor R; Paul L
[Ad] Endereço:Vitreoretina services, Dr. Shroff's Charity Eye Hospital, 5027, Kedarnath Road, Daryaganj, New Delhi, 110002, India. drshalini15@gmail.com.
[Ti] Título:A rare case of scleral buckle infection with Curvularia species.
[So] Source:BMC Ophthalmol;18(1):35, 2018 Feb 09.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Scleral buckling is an established modality of treating retinal detachment. Being an external implant the buckle may be prone to infections. We report such a case with a delayed presentation and a rare etiology. CASE PRESENTATION: A 45 year old male presented with redness, foreign body sensation and discharge for one month in his right eye. The patient had undergone a retinal detachment surgery elsewhere 14 years back without any visual gain. Right eye demonstrated no perception of light and the best corrected visual acuity in the left eye was 6/6, N6. On downgaze an exposed and anteriorly displaced scleral buckle was identified with black deposits and mucopurulent material overlying the buckle. Scleral buckle removal was done. On microbiological examination Curvularia species was identified. Successful treatment with antifungals was done. CONCLUSIONS: Scleral buckle infection with dematiaceous fungi is a rare occurrence. To the best of our knowledge this is the first case report describing a buckle infection caused by the curvularia species.
[Mh] Termos MeSH primário: Ascomicetos/isolamento & purificação
Infecções Oculares Fúngicas/microbiologia
Micoses/microbiologia
Infecções Relacionadas à Prótese/microbiologia
Recurvamento da Esclera/efeitos adversos
[Mh] Termos MeSH secundário: Antibacterianos/uso terapêutico
Antifúngicos/uso terapêutico
Ciprofloxacino/uso terapêutico
Quimioterapia Combinada
Infecções Oculares Fúngicas/diagnóstico
Infecções Oculares Fúngicas/tratamento farmacológico
Fluconazol/uso terapêutico
Seres Humanos
Masculino
Meia-Idade
Micoses/diagnóstico
Micoses/tratamento farmacológico
Infecções Relacionadas à Prótese/diagnóstico
Infecções Relacionadas à Prótese/tratamento farmacológico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 5E8K9I0O4U (Ciprofloxacin); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180211
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-018-0695-4


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[PMID]:29388537
[Au] Autor:Carreira A; Ferreira JB; Pereira I; Ferreira J; Filipe P; Ferreira RB; Monteiro S
[Ad] Endereço:1​CEV, SA, Parque Industrial de Cantanhede/Biocant-Park, lote 120, 3060-197 Cantanhede, Portugal.
[Ti] Título:Blad-containing oligomer: a novel fungicide used in crop protection as an alternative treatment for tinea pedis and tinea versicolor.
[So] Source:J Med Microbiol;67(2):198-207, 2018 Feb.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The lack of novel antifungal drugs and the increasing incidence and severity of fungal infections are major concerns worldwide. Herein, we tested the activity of the Blad-containing oligomer (BCO), a new antifungal molecule already in use for agriculture, on Malassezia spp. and dermatophytes, the causal agents of human tinea versicolor and tinea pedis. Given the lack of a standard method for Malassezia susceptibility testing and the plethora of published methods, we also developed an improved method for this genus. METHODOLOGY: The efficacy of BCO was assessed in vitro and compared to that of the drugs currently utilized in the treatment of tinea versicolor (fluconazole and itraconazole) and tinea pedis (itraconazole and terbinafine). For dermatophytes, the standard microdilution broth-based method was used, with small adjustments, and several broth formulations and inocula sizes were tested to develop an improved susceptibility method for Malassezia spp. RESULTS: We successfully developed a microdilution broth-based method with considerable advantages over other available methods, and used it for all in vitro susceptibility tests of Malassezia spp. isolates. We report that, on a molar basis, BCO was more effective than fluconazole or itraconazole on most strains of Malassezia spp. isolated from clinical samples (n=29). By contrast, BCO was less effective than itraconazole or terbinafine on the common dermatophytes Trichophyton rubrum and Trichophyton interdigitale. CONCLUSION: These data place BCO as a promising drug for the treatment of Malassezia-associated skin diseases. Further in vivo studies are now required to ascertain its applicability in the clinical setting.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Arthrodermataceae/efeitos dos fármacos
Fungicidas Industriais/farmacologia
Malassezia/efeitos dos fármacos
Tinha dos Pés/tratamento farmacológico
Tinha Versicolor/tratamento farmacológico
[Mh] Termos MeSH secundário: Antifúngicos/uso terapêutico
Proteção de Cultivos
Descoberta de Drogas
Fluconazol/farmacologia
Fungicidas Industriais/uso terapêutico
Seres Humanos
Itraconazol/farmacologia
Testes de Sensibilidade Microbiana
Tinha dos Pés/microbiologia
Tinha Versicolor/microbiologia
Trichophyton/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Fungicides, Industrial); 304NUG5GF4 (Itraconazole); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000675


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[PMID]:29241891
[Au] Autor:Pagès A; Iriart X; Molinier L; Georges B; Berry A; Massip P; Juillard-Condat B
[Ad] Endereço:CHU de Toulouse, Pharmacie, Toulouse, France. Electronic address: pages.ar@chu-toulouse.fr.
[Ti] Título:Cost Effectiveness of Candida Polymerase Chain Reaction Detection and Empirical Antifungal Treatment among Patients with Suspected Fungal Peritonitis in the Intensive Care Unit.
[So] Source:Value Health;20(10):1319-1328, 2017 12.
[Is] ISSN:1524-4733
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Mortality from intra-abdominal candidiasis in intensive care units (ICUs) is high. It takes many days for peritoneal-fluid fungal culture to become positive, and the recommended empirical antifungal therapy involves excessive costs. Polymerase chain reaction (PCR) should produce results more rapidly than fungal culture. OBJECTIVES: To perform a cost-effectiveness analysis of the combination of several diagnostic and therapeutic strategies to manage Candida peritonitis in non-neutropenic adult patients in ICUs. METHODS: We constructed a decision tree model to evaluate the cost effectiveness. Cost and effectiveness were taken into account in a 1-year time horizon and from the French National Health Insurance perspective. Six strategies were compared: fluconazole or echinocandin as an empirical therapy, plus diagnosis by fungal culture or detection by PCR of all Candida species, or use of PCR to detect most fluconazole-resistant Candida species (i.e., Candida krusei and Candida glabrata). RESULTS: The use of fluconazole empirical treatment and PCR to detect all Candida species is more cost effective than using fluconazole empirical treatment without PCR (incremental cost-effectiveness ratio of €40,055/quality-adjusted life-year). Empirical treatment with echinocandin plus PCR to detect C. krusei and C. glabrata is the most effective strategy, but has an incremental cost-effectiveness ratio of €93,776/quality-adjusted life-year. If the cost of echinocandin decreases, then strategies involving PCR plus empirical echinocandin become more cost-effective. CONCLUSIONS: Detection by PCR of all Candida species and of most fluconazole-resistant Candida species could improve the cost-effectiveness of fluconazole and echinocandin given to non-neutropenic patients with suspected peritoneal candidiasis in ICUs.
[Mh] Termos MeSH primário: Antifúngicos/administração & dosagem
Candida/isolamento & purificação
Candidíase/diagnóstico
Peritonite/diagnóstico
Reação em Cadeia da Polimerase/métodos
[Mh] Termos MeSH secundário: Adulto
Antifúngicos/economia
Candidíase/tratamento farmacológico
Candidíase/microbiologia
Análise Custo-Benefício
Árvores de Decisões
Farmacorresistência Fúngica
Equinocandinas/administração & dosagem
Equinocandinas/economia
Fluconazol/administração & dosagem
Fluconazol/economia
Seres Humanos
Unidades de Terapia Intensiva
Peritonite/tratamento farmacológico
Peritonite/microbiologia
Reação em Cadeia da Polimerase/economia
Anos de Vida Ajustados por Qualidade de Vida
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Echinocandins); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


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[PMID]:29214970
[Au] Autor:Kassi FK; Bellet V; Drakulovski P; Krasteva D; Roger F; Valérie BA; Aboubakar T; Doumbia A; Kouakou GA; Delaporte E; Reynes J; Yavo W; Menan HIE; Bertout S
[Ad] Endereço:1​Laboratoire de Parasitologie et de Mycologie - CeDReS (Centre de Diagnostic et de Recherche sur le SIDA et les Autres Maladies Infectieuses), UFR Pharmacie, CHU de Treichville, Université Félix Houphouët Boigny, Abidjan, Ivory Coast.
[Ti] Título:Comparative typing analyses of clinical and environmental strains of the Cryptococcus neoformans/Cryptococcus gattii species complex from Ivory Coast.
[So] Source:J Med Microbiol;67(1):87-96, 2018 Jan.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The aim of this study was to assess the biotope of the Cryptococcus neoformans/Cryptococcus gattii species complex from Ivory Coast, and clarify the possible epidemiological relationship between environmental and clinical strains. METHODOLOGY: Samples from Eucalyptus camaldulensis (n=136), Mangifera indica (n=13) and pigeon droppings (n=518) were collected from different sites close to the living environment of Ivorian HIV patients with cryptococcosis (n=10, 50 clinical strains). Clinical and environmental strains were characterized by molecular serotyping and genotyping [RFLP analysis of the URA5 gene, (GACA)4, (GTG)5 and M13 PCR fingerprinting] and compared.Results/Key findings. Environmental strains were recovered only from the pigeon droppings. In vitro susceptibility profiles showed that all strains were susceptible to fluconazole, flucytosine and amphotericin B. All environmental strains consisted of C. neoformans (A, AFLP1/VNI), whereas clinical strains included C. neoformans (A, AFLP1/VNI), C. neoformans x Cryptococcus deneoformans hybrids (AD, AFLP3/VNIII) and Cryptococcus deuterogattii (B, AFLP6/VGII). Two patients were co-infected with both C. neoformans and C. neoformans x C. deneoformans hybrids. We noticed a low genetic diversity among the environmental samples compared to the high diversity of the clinical samples. Some clinical strains were genetically more similar to environmental strains than to other clinical strains, including those from the same patient. CONCLUSION: These results provide new information on the ecology and epidemiology of the C. neoformans/C. gattii species complex in Ivory Coast.
[Mh] Termos MeSH primário: Cryptococcus gattii/genética
Cryptococcus neoformans/genética
[Mh] Termos MeSH secundário: Adulto
Anfotericina B/uso terapêutico
Antifúngicos/uso terapêutico
Cloranfenicol/uso terapêutico
Costa do Marfim
Criptococose/microbiologia
DNA Fúngico/genética
Microbiologia Ambiental
Feminino
Fluconazol/uso terapêutico
Flucitosina/uso terapêutico
Genótipo
Infecções por HIV/microbiologia
Seres Humanos
Masculino
Testes de Sensibilidade Microbiana/métodos
Meia-Idade
Tipagem Molecular/métodos
Técnicas de Tipagem Micológica/métodos
Estudos Prospectivos
Sorotipagem/métodos
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (DNA, Fungal); 66974FR9Q1 (Chloramphenicol); 7XU7A7DROE (Amphotericin B); 8VZV102JFY (Fluconazole); D83282DT06 (Flucytosine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000654


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[PMID]:29187956
[Au] Autor:Elmehdi E; Zerkly B
[Ad] Endereço:Service de Traumatologie Orthopedie du Groupe Hospitalier Publique du Sud de l'Oise(GHPSO), bp60100 Creil, France.
[Ti] Título:[Leg ulcer revealing cutaneous leishmaniasis].
[Ti] Título:Ulcère de jambe révélant la leishmaniose cutanée..
[So] Source:Pan Afr Med J;27:287, 2017.
[Is] ISSN:1937-8688
[Cp] País de publicação:Uganda
[La] Idioma:fre
[Ab] Resumo:Leishmaniases are parasitic diseases occurring in endemic tropical and subtropical areas and caused by protozoa of the genus leishmania, transmitted by a diptera (sand fly). We here report a case of topical cutaneous leishmaniasis discovered in a 15-year old boy with painless ulcer on his left leg, who had been staying in South Africa. Clinical examination showed painless non-itchy ulcer, occurred 1 month before, on the antero-internal part of his left leg with crusts and scars caused by insect bites, all evolving in a context of patient's general health status, without mucosal or visceral lesions. Skin biopsy allowed specific parasitologic diagnosis revealing topical zoonotic cutaneous leishmaniasis caused by L. major. The patient underwent topical treatment based on paramomycin and oral fluconazole resulting in ulcer healing at the end of 2 months.
[Mh] Termos MeSH primário: Úlcera da Perna/diagnóstico
Leishmaniose Cutânea/diagnóstico
Zoonoses/diagnóstico
[Mh] Termos MeSH secundário: Administração Tópica
Adolescente
Animais
Antiparasitários/administração & dosagem
Biópsia
Fluconazol/administração & dosagem
Seres Humanos
Úlcera da Perna/tratamento farmacológico
Úlcera da Perna/parasitologia
Leishmania major/isolamento & purificação
Leishmaniose Cutânea/tratamento farmacológico
Leishmaniose Cutânea/patologia
Masculino
Paromomicina/administração & dosagem
Resultado do Tratamento
Zoonoses/tratamento farmacológico
Zoonoses/parasitologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiparasitic Agents); 61JJC8N5ZK (Paromomycin); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.11604/pamj.2017.27.287.13090


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[PMID]:28457069
[Au] Autor:Kriem S; Peretz A; Blum A
[Ad] Endereço:Department of Medicine, Padeh Poria Medical Center, Tiberias, affiliated with Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel.
[Ti] Título:Lingua Villosa Nigra.
[So] Source:Isr Med Assoc J;19(2):131, 2017 Feb.
[Is] ISSN:1565-1088
[Cp] País de publicação:Israel
[La] Idioma:eng
[Mh] Termos MeSH primário: Candida albicans/isolamento & purificação
Candidíase Bucal
Fluconazol/administração & dosagem
Língua Pilosa
[Mh] Termos MeSH secundário: Administração Tópica
Idoso de 80 Anos ou mais
Antifúngicos/administração & dosagem
Candidíase Bucal/complicações
Candidíase Bucal/diagnóstico
Candidíase Bucal/tratamento farmacológico
Candidíase Bucal/fisiopatologia
Feminino
Seres Humanos
Língua Pilosa/diagnóstico
Língua Pilosa/tratamento farmacológico
Língua Pilosa/etiologia
Língua Pilosa/fisiopatologia
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171130
[Lr] Data última revisão:
171130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:28966274
[Au] Autor:Zhong Y; Han X; Li S; Qi H; Song Y; Qiao X
[Ad] Endereço:Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University.
[Ti] Título:Design, Synthesis, Antifungal Activity and Molecular Docking of Thiochroman-4-one Derivatives.
[So] Source:Chem Pharm Bull (Tokyo);65(10):904-910, 2017.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:N-Myristoyltransferase (NMT) has been validated pre-clinically as a target for treatment of fungal infections. Various substituted thiochroman-4-one derivatives have been synthesized by an efficient method. The synthesized compounds 7a-y and 8a-t were evaluated for their in vitro antifungal activity against the Canidia albicans, Cryptococcus neoformans, Epidermophyton floccosum, Mucor racemosus, Microsporum gypseum and Aspergillus nigerstrain. A series of compounds exhibited significant activity (minimal inhibitory concentrotion (MIC)=0.5-16 µg/mL) against Canidia albicans and Cryptococcus neoformans. The antifungal activity of compound 7b was reached to that of fluconazole, which can serve as a good starting point for further studies of structural diversity of the NMT inhibitors. The molecular docking studies revealed an interesting binding profile with very high receptor affinity for NMT of Canidia albicans.
[Mh] Termos MeSH primário: Aciltransferases/metabolismo
Antifúngicos/síntese química
Cromanos/química
Desenho de Drogas
Inibidores Enzimáticos/síntese química
[Mh] Termos MeSH secundário: Aciltransferases/química
Antifúngicos/química
Antifúngicos/farmacologia
Sítios de Ligação
Candida albicans/efeitos dos fármacos
Domínio Catalítico
Cromanos/síntese química
Cromanos/farmacologia
Cryptococcus neoformans/efeitos dos fármacos
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Fluconazol/farmacologia
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Chromans); 0 (Enzyme Inhibitors); 8VZV102JFY (Fluconazole); EC 2.3.- (Acyltransferases); EC 2.3.1.97 (glycylpeptide N-tetradecanoyltransferase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c17-00274


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[PMID]:28874321
[Au] Autor:Cai Z; Ding Z; Hao Y; Ni T; Xie F; Zhao J; Li R; Yu S; Wang T; Chai X; Jin Y; Gao Y; Zhang D; Jiang Y
[Ad] Endereço:Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
[Ti] Título:Design, synthesis, and SAR study of 3-(benzo[d][1,3]dioxol-5-yl)-N-benzylpropanamide as novel potent synergists against fluconazole-resistant Candida albicans.
[So] Source:Bioorg Med Chem Lett;27(19):4571-4575, 2017 10 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Based on our previous discovery and SAR study on the lead compounds 7d, 5 and berberine which can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, a series of 3-(benzo[d][1,3]dioxol-5-yl)-N-(substituted benzyl)propanamides were designed, synthesized, and evaluated for their in vitro synergistic activity in combination with fluconazole. The series 2a-f were designed by replacing the amide moiety of the lead compound 7d with retro-amide moiety, and compounds 2a and 2b showed more activity than the lead 7d. Furthermore, introducing biphenyl moiety into series 2d-f afforded series 3a-r, most of which exhibited significantly superior activity to the series 2d-f. Especially, compound 3e, at a concentration of 1.0µg/ml, can enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans from 128.0µg/ml to 0.125-0.25µg/ml. A clear SAR of the compounds is discussed.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Benzodioxóis/farmacologia
Candida albicans/efeitos dos fármacos
Desenho de Drogas
Fluconazol/farmacologia
[Mh] Termos MeSH secundário: Antifúngicos/síntese química
Antifúngicos/química
Benzodioxóis/síntese química
Benzodioxóis/química
Relação Dose-Resposta a Droga
Testes de Sensibilidade Microbiana
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (3-(benzo(d)(1,3)dioxol-5-yl)-N-benzylpropanamide); 0 (Antifungal Agents); 0 (Benzodioxoles); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE



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