RESUMO
Social insects are in mutualism with microorganisms, contributing to their resistance against infectious diseases. The fungus Pseudallescheria boydii SNB-CN85 isolated from termites produces ovalicin derivatives resulting from the esterification of the less hindered site of the ovalicin epoxide by long-chain fatty acids. Their structures were elucidated using spectroscopic analysis and semisynthesis from ovalicin. For ovalicin, these compounds displayed antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei, with IC50 values of 19.8 and 1.1 µM, respectively, for the most active compound, i.e., ovalicin linoleate. In parallel, metabolomic profiling of a collection of P. boydii strains associated with termites made it possible to highlight this class of compounds together with tyroscherin derivatives in all strains. Finally, the complete genome of P. boydii strains was obtained by sequencing, and the cluster of potential ovalicin and ovalicin biosynthesis genes was annotated. Through these metabolomic and genomic analyses, a new ovalicin derivative named boyden C, in which the 6-membered ring of ovalicin was opened by oxidative cleavage, was isolated and structurally characterized.
Assuntos
Antimaláricos , Isópteros/microbiologia , Plasmodium falciparum/crescimento & desenvolvimento , Scedosporium , Sesquiterpenos , Tripanossomicidas , Trypanosoma brucei brucei/crescimento & desenvolvimento , Animais , Antimaláricos/química , Antimaláricos/farmacologia , Guiana Francesa , Scedosporium/química , Scedosporium/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologiaRESUMO
The chemical diversity of biologically active fungal strains from 42 Colletotrichum, isolated from leaves of the tropical palm species Astrocaryum sciophilum collected in pristine forests of French Guiana, was investigated. The collection was first classified based on protein fingerprints acquired by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) correlated with cytotoxicity. Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS) data from ethyl acetate extracts were acquired and processed to generate a massive molecular network (MN) using the MetGem software. From five Colletotrichum strains producing cytotoxic specialized metabolites, we predicted the occurrence of peptide and cytochalasin analogues in four of them by MN, including a similar ion clusters in the MN algorithm provided by MetGem software. Chemoinformatics predictions were fully confirmed after isolation of three pentacyclopeptides (cyclo(Phe-Leu-Leu-Leu-Val), cyclo(Phe-Leu-Leu-Leu-Leu) and cyclo(Phe-Leu-Leu-Leu-Ile)) and two cytochalasins (cytochalasin C and cytochalasin D) exhibiting cytotoxicity at the micromolar concentration. Finally, the chemical study of the last active cytotoxic strain BSNB-0583 led to the isolation of four colletamides bearing an identical decadienamide chain.
Assuntos
Colletotrichum/metabolismo , Algoritmos , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Guiana Francesa , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em TandemRESUMO
PURPOSE: To analyze the evolution profiles of several corneal topographic and tomographic parameters in progressive keratoconus and compare them with the kinetics of evolution of anterior keratometry. METHODS: One hundred nine eyes of 55 patients were prospectively enrolled and followed up every 3 months for at least 1 year. Forty-five corneal parameters were measured at each visit using a combined Placido-based and dual Scheimpflug imaging system. Percentage of progression between each visit was calculated for each parameter and comparisons were tested between the different variables. RESULTS: At 1 year, 11% (12/109) of eyes progressed with an increase in maximum anterior keratometry of 1 D or more. Among these eyes, the posterior maximum keratometry and vertical corneal coma had a significantly higher percentage of progression (P < 0.05) than the maximum anterior keratometry, 5.9%, 27%, and 3.2%, respectively, and occurred significantly earlier than the modifications of the anterior keratometry, at the third-, sixth-, and 12th-month visits, for vertical corneal coma, posterior keratometry, and anterior keratometry respectively. CONCLUSIONS: Modifications of the posterior surface and corneal vertical coma occurred earlier and were detectable before changes in the anterior keratometry readings in eyes with progressive keratoconus. These parameters may be relevant warning signs when monitoring progressive keratoconus.
Assuntos
Córnea/patologia , Ceratocone/diagnóstico , Adolescente , Adulto , Paquimetria Corneana , Topografia da Córnea , Aberrações de Frente de Onda da Córnea/diagnóstico , Diagnóstico por Imagem/métodos , Progressão da Doença , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto JovemRESUMO
PURPOSE: To evaluate the corneal thickness and curvature of myopic and patients with keratoconus from two countries. METHODS: This cross-sectional study was conducted at Cabinet Opale, Fort de France, French West Indies and University Hospital of Bordeaux, France. Corneal thickness and curvature were assessed in 170 keratoconic eyes of 89 residents of the French Caribbean Islands (FCI) and 159 keratoconic eyes of 91 residents of the Aquitaine region of southwest France. A group of age-matched keratoconus-free patients who had been referred for refractive surgery owing to myopia (173 FCI [173 eyes; 87 individuals] and Aquitaine [181 eyes; 93 individuals]) were also assessed. RESULTS: The mean age at keratoconus diagnosis was significantly higher among FCI than Aquitaine residents (p = 0.009). The mean keratometric (Km) reading was statistically higher for keratoconic FCI than Aquitaine patients, at 48.06 versus 46.21 diopters (p = 0.001). This difference was more pronounced among patients aged >40 years than those ≤40 years (p = 0.009). Patients with keratoconus showed no significant difference in mean central corneal thickness and thinnest corneal point values, irrespective of region. Myopic individuals from the FCI, however, had significantly lower mean central corneal thickness and thinnest corneal point measurements than Aquitaine myopics, irrespective of age group (p ≤ 0.0008). CONCLUSION: The corneas of patients with keratoconus of African-Caribbean and Caucasian origins are of similar thickness. Myopic African-Caribbean patients referred for refractive surgery tend to present with thinner corneas than Caucasians.