O fungo Aspergillus flavus isolado como endofítico da planta Paspalum maritimum Trin. foi avaliado quanto ao seu potencial de aplicação em reações de biotransformações. Os compostos chalcona (1), 3,4,5-trimetoxichalcona (2) e 2,3,4,4'-tetrametoxichalcona (3) foram biotransformados, respectivamente, na diidrochalcona (4), 3,4,5-trimetoxidiidrochalcona (5) e 2,3,4,4'-tetrametoxidiidrochalcona (6). As estruturas destes compostos foram determinadas por análises de RMN uni e bidimensionais e por espectrometria de massas. As diidrochalconas 5 e 6 são substâncias inéditas. The fungus Aspergillus flavus isolated as endophytic of the plant Paspalum maritimumTrin. was evaluated for its potential application in biotransformation reactions. The compounds chalcone (1), 3,4,5-trimethoxychalcone (2) and 2,3,4,4'-tetramethoxychalcone (3) were biotransformed, respectively, in dihydrochalcone (4), 3,4,5-trimethoxydihydrochalcone (5) and 2,3,4,4'-tetramethoxydihydrochalcone (6). The structures were elucidated by spectroscopic methods including 1D and 2D NMR techniques, and MS analysis. The dihydrochalcones 5 and 6 are new compounds.

Antibiotic resistance results in higher medical costs, prolonged hospital stays and increased mortality and is rising to dangerously high levels in all parts of the world. Therefore, this study aims to search for new antimicrobial agents through bioprospecting of extracts of endophytic fungi from Bauhinia guianensis, a typical Amazonian plant used in combating infections. Seventeen (17) fungi were isolated and as result the methanolic extract of the fungus Exserohilum rostratum showed good activity against the bacteria tested. The polyketide monocerin was isolated by the chromatographic technique, identified by NMR and MS, showing broad antimicrobial spectrum.

IntroductionCancer and corresponding available treatments are associated with substantial symptoms and functional limitations. In this context, collection of patient-reported outcomes (PRO) in clinical trials gained special interest and is recommended by regulatory authorities. Within clinical trials framework, PRO may provide evidence to support medicines approval, labeling and marketing claims. This study aims to analyze the existing evidence based on PRO as part of new oncology indications receiving positive opinions issued by the European Medicines Agency (EMA) between 2017 and 2020 and to identify PRO related label claims granted.MethodologyOncology medicinal products and indications approved by the European Commission following a positive opinion from the EMA between 2017 and 2020 were identified. European Public Assessment Report (EPAR) and Summary of Product Characteristics (SmPC) were reviewed for each medicinal product to identify use of PRO and PRO label claims.ResultsA total of 128 oncology indications, corresponding to 76 medicines, were approved; of those, 100 (78.1%) included PRO in the confirmatory clinical trials. Thirty-seven indications were supported by double-blind randomized trials and the remainder 63 by open-label trials. Out of the 104 confirmatory trials analyzed, PRO were defined as a secondary endpoint in 60 studies (57.7%), exploratory in 31 (29.8%) and as both in 13 (12.5%). In total, 54 different PRO measures (PROM) were used, of those 41 (75.9%) were disease-specific measures. Nevertheless, PROM selected relied on the EORTC (41.3%), FACIT (17.1%) and EQ-5D (29.2%) measures. A total of 76 indications (59.4%) had PRO reviewers comments included in the EPAR, however only 22 indications (17.8%) included label claims in the SmPC. The reasons identified in the EMA assessment supporting the exclusion of PRO claims were described for 34 indications (44.7%).ConclusionsDespite growing recognition of the value of PRO data for the development of improved cancer therapies, PRO implementation remains challenging. The main reasons identified in our study are related with study design, missing data, study conduct and PROM selection.

Foram isoladas e identificadas duas neolignanas: a surinamensina e a virolina. A tendência geral observada nos resultados foi de aumento da intensidade dos efeitos alelopáticos inibitórios em função do aumento da concentração, com inibições máximas obtidas, sempre, na concentração de 8,0 mg L -1 . A surinamensina apresentou maior potencial para inibir a germinação e o desenvolvimento da radícula e do hipocótilo do que a virolina, independentemente da espécie receptora e do fator da planta analisado. Considerando-se as intensidades dos efeitos promovidos sobre os três fatores das plantas, o desenvolvimento da radícula e o do hipocótilo foram mais intensamente inibidos pelas duas substâncias do que a germinação das sementes. À exceção dos efeitos verificados sobre o desenvolvimento do hipocótilo, malícia foi a espécie de maior sensibilidade aos efeitos alelopáticos das duas neolignanas, enquanto mata-pasto foi aquela que evidenciou inibições de menor magnitude.Palavras-chave: alelopatia, inibição, planta daninha, surinamensina, virolina. ABSTRACT -The objective of this research was to isolate, identify and characterize the allelopathic activity of chemical compounds in Virola surinamensis leaves. The process of isolation and identification of chemicals compounds involved the use of organic solvents and Magnetic Nuclear

The paper describes the isolation of ergosterol peroxide, monocerin, annularin I and annularin J compounds of Exserohilum rostratum biomass extracts. Compounds were isolated by silica gel column chromatography in polarity gradient and the structures were determined by nuclear magnetic resonance (NMR) and mass spectrometry (MS) methods. Monocerin, annularin I and annularin J compounds were tested against Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis bacteria and showed moderate activity. Annularin I and annularin J compounds are new natural products. Keywords: annularins, polyketides, E. rostratum, endophytic fungi IntroductionEndophytic microorganisms live in plants internal tissues without causing apparent disease to their hosts. 1 Endophyte microbial colonization can be demonstrated by isolating plant tissues disinfected through histological cut and by DNA amplification technique. 2 In tropical and temperate forests (which cover only 1.5% of the terrestrial surface), there are approximately 300,000 (three hundred thousand) plant species analyzed so far, homing more than 60% of the world's biodiversity. 3 Extreme diversity allows for the opportunity to discover new microorganisms that may be potential bioactive compounds producers for agriculture, industry and medicine. 4 There is a great interest in the study of endophytic microorganisms, including their application in pest biocontrol. Fungi are good secondary metabolite producers, and many have the same biological activity, 5-8 especially polyketides. For example, the polyketide citrinin isolated from Penicillium janthinellum completely inhibited the growth of Leishmania braziliensis.9 Some fungi species of Penicillium and Pestalotiopsis genera produce high diversity of polyketides with antimicrobial activity. 10,11In another study with a variety of endophytes isolated from Vigueira arenaria and Tithonia diversifolia fungal extracts, important antiparasitic and antimicrobial activities were observed in fungal extracts. 12 In the Nodulisporium sp. (Xylariaceae) fungus extract, which was isolated from the woody plant species Erica arborea (Ericaceae), nodulisporina D, E and F compounds were obtained, having antifungal, antibacterial and algaecide activity.13 From the endophytic fungus Ampelomyces sp., isolated from the medicinal plant Urospermum picroides (Asteraceae), 6-O-methylalaternina and altersolanol A compounds were isolated, which showed antimicrobial activity against Gram-positive pathogens Staphylococcus aureus, S. epidermidis and Enteorococcus faecalis.14 Brazil is estimated to be home of about 20% of the world's biodiversity and is considered the country in the world with the largest number of endemic species.15 About 270,000 plant species on this planet are estimated to harbor about 13.6 million unique endophytic fungal species, in addition to approximately 100,000 fungi species already known to date. Therefore, there are great chances of finding Pinheiro et al. 1433 Vol. 27, No. 8, 2016 new substances produced by endophytic fun...