Geisa Paulino Caprini Evaristo

In light of the multi-drug resistance of Acinetobacter baumannii to commercially available antibiotics, the search for new effective molecules against this bacterium is fundamental. In this study, metabolites present in the skin secretion of the anuran Phyllomedusa camba were identified using mass spectrometry. Among the molecules of interest found in the skin secretion of the anuran, 147 were tested in silico via molecular docking against the penicillin-binding protein and the 30S ribosome targets of A. baumannii. The molecular docking results indicated promising molecules against A. baumannii. In vitro assays were conducted to evaluate the antimicrobial activity of the crude skin secretion of P. camba against the standard strain of A. baumannii (ATCC 19606). The results showed antimicrobial activity for the secretion of P. camba, with a minimum inhibitory concentration (MIC) of 50 µg/mL and an IC50 of 28.65 µg/mL. Compared to results found in the literature, the obtained MIC and IC50 values appear promising. Bioprospecting in anurans presents itself as an alternative for the discovery of new drugs against multi-resistant bacteria.

A resina aromática das espécies do gênero Protium é utilizada na medicina popular como vermífugo, antiparasitário, ansiolítico, cicatrizante e como matéria-prima para o tratamento de problemas respiratórios, dentários e digestivos. A espécie Protium calendulinum Daly produz resina em forma de gotas que cristalizam quando em contato com o ambiente, sendo também rica em óleo essencial. Os estudos para avaliar a composição química do óleo essencial da resina e potenciais atividades biológicas da P. calendulinum frente à microrganismo, ainda são incipientes. Portanto, o presente trabalho teve por objetivo analisar a composição química de seu óleo essencial, bem como avaliar suas possíveis atividades bactericida e leishmanicida. A análise da composição química do óleo demonstrou a presença de monoterpenos (82,64%) e sesquiterpenos (2,07%). Os compostos majoritários foram o orto-cimeno (27,52 %), α-felandreno (17,73 %), α-pineno (13,77 %), eucaliptol (6,47 %) e α-terpineno (5,97 %). O óleo essencial usado in natura demonstrou atividade bactericida em teste de difusão em disco para as espécies Staphylococcus. aureus, Staphylococcus. aureus Resistente a Meticilina (MRSA), Enterococcus faecalis, Pseudomonas aeruginosa e Klebsiella pneumoniae, com zonas de inibição de crescimento bacteriano entre 7,7 e 14,0 mm, porém, não indicou atividade frente às espécies Escherichia coli e Acinetobacter baumannii. Atividade leishmanicida frente à forma promastigota da Leishmania amazonensis foi observada nas concentrações de 100 µg.mL-1 (Índice de Inibição de Crescimento de 93%) e 200 µg.mL-1 (Índice de Inibição de Crescimento de 100%). A CIM observada foi de 100 µg.mL-1 e CI50 de 96,08 µg.mL-1.

Capirona macrophylla is a Rubiaceae known as “mulateiro”. Ethnobotanical extracts have been used for skin treatment and in the management of leishmaniasis and malaria. Objectives: The metabolites in aqueous extracts from wood bark, leaves, and stems were identified, and their in silico docking and in vitro cellular efficacy against Leishmania amazonensis and Plasmodium falciparum were evaluated. Methods: The extracts were analyzed by UHPLC/HRMSⁿ using untargeted metabolomics approach with MSDial, MSFinder, and GNPS software for metabolite identification and spectra clustering. The most abundant metabolites underwent molecular docking using AutoDock via PyRx, targeting the dihydroorotate dehydrogenase from Leishmania and P. falciparum, and evaluated through molecular dynamics simulations using Gromacs. In vitro biological assays were conducted on 60 HPLC-fractions against these parasites. Results: Metabolomics analysis identified 5100 metabolites in ESI+ and 2839 in ESI− spectra among the “mulateiro” samples. GNPS clustering highlighted large clusters of quercetin and chlorogenic acid groups. The most abundant metabolites were isofraxidin, scopoletin, 5(S)-5-carboxystrictosidine, loliolide, quercetin, quinic acid, caffeoylquinic acid (and isomers), chlorogenic acid, neochlorogenic acid, tryptophan, N-acetyltryptophan, epicatechin, procyanidin, and kaempferol-3-O-robinoside-7-O-rhamnoside. Molecular docking pointed to 3,4-dicaffeoylquinic acid and kaempferol as promising inhibitors. The in vitro assays yielded four active HPLC-fractions against L. amazonensis with IC50 values ranging from 175.2 μg/mL to 194.8 μg/mL, and fraction G29 showed an IC50 of 119.8 μg/mL against P. falciparum. Conclusions: The ethnobotanical use of “mulateiro” wood bark tea as an antimalarial and antileishmanial agent was confirmed through in vitro assays. We speculate that these activities are attributed to linoleic acids and quinic acids.

A Bertholletia excelsa, conhecida popularmente como castanheira, tem grande importância na economia da região Amazônica e para as comunidades tradicionais, sendo utilizada também na medicina popular como infusão para tratamentos de diarréia, menopausa, diabetes, inflamação e como antibiótico. O objetivo geral deste estudo é identificar os principais metabólitos secundários presente na casca tronco da Bertholletia excelsa utilizando a técnica de análise metabolômica pela alta capacidade de extração, detecção analítica e sensibilidade. A coleta das cascas do tronco, foi realizada no Campo Experimental da Embrapa em Porto Velho/RO localizado na Rodovia BR 364 Km 55 em 06/08/2020. Exsicata do material coletado foi depositada para identificação taxonômica no Herbário Rondoniense João Geraldo Kuhlmann. Dentre os metabólitos identificados, os de maior concentração foram: ácido gálico, epigalocatequina, ácido linoleico, ácido octadecadienóico, ácido α-eleostárico, ácido 4-acetamidobutanóico, ácido 9-oxo-octadeca-10,12-dienóico, pirogalol e colina.

This narrative review aims to update the ethnopharmacology, phytochemistry and biological activities of Geissospermum species described in the literature, in order to contribute to the knowledge of bioactive compounds of therapeutic interest and establish directions for future research with this genus. The term “Geissospermum” was used to perform searches in different databases such as NDLTD (Digital Library Network of Theses and Dissertations), Google Scholar, PubChem, Scifinder, Web of Science, SciELO, PubMed and Science Direct. Google's National Institute of Industrial Property and Patents (INPI) was also consulted. The keywords indole alkaloids, quina-quina, Geissospermum, Geissospermum reticulatum and malaria were used in the search. Publications in Portuguese, French, Spanish and English published between 1950 and 2022 were included. Indole alkaloids are the main secondary metabolites found in this genus, and several molecules have already been isolated, which may be related to the described pharmacological activities. Extracts and isolated compounds showed antitumor, antimalarial, antinociceptive, anti-inflammatory, anticholinesterase, anti-HIV, antimicrobial and antioxidant activity. Plants of the genus Geissospermum are used in Brazil mainly by the Amazonian peoples to treat various pathologies. Biological activities reported for extracts and isolated compounds are consistent with etonopharmacological use against malaria, cancer and other diseases. Future work with Geissospermum species is needed to elucidate the mechanism of action of the isolated alkaloids, as well as their toxicological profile.

White-rot fungi are efficient degraders of the lignin moiety due to the production of extracellular enzymes that includes the laccases which are able to depolymerize lignin oxidative processes to low-molecular weight phenolic and aromatic compounds. These end-products have important industrial applications, as building blocks for chemical syntheses of high-value. Thus, the objective of this work was to optimize the culture conditions for laccase production by Pleurotus ostreatus Florida grown on Kraft lignin, and to evaluate lignin biodegradation products. The fungal strain produced optimum laccase titers after evaluation in a 3³-factorial statistical design by varying: lignin concentration, yeast extract and time of cultivation. The extracellular fluid obtained under the optimized culture condition was treated by liquid-liquid partition with ethyl acetate in order to determine the lignin degradation products by LC-MS/MS. Concentration of lignin was the main variable that increased laccase production assayed against substrate 2,6-dimethoxyphenol. Optimal laccase production predicted by the model was 5.73 U/mL under the condition: 0.87% (w/v) lignin, 4.5% (w/v) yeast extract and 10 days cultivation. The experimental laccase titer obtained following optimal conditions was 5.68 U/mL. The lignin metabolites identified were 4-methoxycinnamaldehyde and cuminaldehyde. In addition, abscisic acid was produced; considered a stress-related hormone product of the fungus. These findings show a suitable source of fungal laccase for obtaining new metabolites from the biodegradation of Kraft lignin by fermentation.