RESUMO
This study presents an innovative method for synthesizing ß-amino carbonylated compounds, specifically 2-[phenyl(phenylamino)methyl] cyclohexanone, achieving high conversions and diastereomeric ratios. Using trypsin or α-chymotrypsin in both free and immobilized forms on titanate nanotubes (NtsTi), synthesized through alkaline hydrothermal methods, successful immobilization yields were attained. Notably, α-chymotrypsin, when free, displayed a diastereoselective synthesis of the anti-isomer with 97 % conversion and 16 : 84 (syn : anti) diastereomeric ratio, which slightly decreased upon immobilization on NtsTi. Trypsin, in its free form, exhibited diastereoselective recognition of the syn-isomer, while immobilization on NtsTi (trypsin/NtsTi) led to an inversion of diastereomeric ratio. Both trypsin/NtsTi and α-chymotrypsin/NtsTi demonstrated significant catalytic efficiency over five cycles. In conclusion, NtsTi serves as an effective support for trypsin and α-chymotrypsin immobilization, presenting promising prospects for diastereoselective synthesis and potential industrial applications. Furthermore, it offers promising prospects for the diastereoselective synthesis of 2-[phenyl(phenylamino)methyl] cyclohexanone through multicomponent Mannich reaction and future industrial application.
Assuntos
Quimotripsina , Enzimas Imobilizadas , Nanotubos , Titânio , Tripsina , Titânio/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Quimotripsina/química , Quimotripsina/metabolismo , Tripsina/metabolismo , Tripsina/química , Nanotubos/química , Estereoisomerismo , Biocatálise , Cicloexanonas/químicaRESUMO
Botrytis cinerea, Rhizoctonia solani and Hemileia vastatrix are three species of phytopathogenic fungi behind major crop losses worldwide. These have been selected as target models for testing the fungicide potential of a series of bis(ylidene) cyclohexanones. Although some compounds of this chemical class are known to have inhibitory activity against human pathogens, they have never been explored for the control of phytopathogens until now. In the present work, bis(ylidene) cyclohexanones were synthesized through simple, fast and low-cost base- or acid-catalyzed aldol condensation reaction and tested in vitro against B. cinerea, R. solani and H. vastatrix. bis(pyridylmethylene) cyclohexanones showed the highest activity against the target fungi. When tested at 200 nmol per mycelial plug against R. solani., these compounds completely inhibited the mycelial growth, and the most active bis(pyridylmethylene) cyclohexanone compound had an IC50 of 155.5 nmol plug-1. Additionally, bis(pyridylmethylene) cyclohexanones completely inhibited urediniospore germination of H. vastatrix, at 125 µmol L-1. The most active bis(pyridylmethylene) cyclohexanone had an IC50 value of 4.8 µmol L-1, which was estimated as approximately 2.6 times lower than that found for the copper oxychloride-based fungicide, used as control. Additionally, these substances had a low cytotoxicity against the mammalian Vero cell line. Finally, in silico calculations indicated that these compounds present physicochemical parameters regarded as suitable for agrochemicals. Bis(ylidene) cyclohexanones may constitute promising candidates for the development of novel antifungal agents for the control of relevant fungal diseases in agriculture.
Assuntos
Antifúngicos , Fungicidas Industriais , Humanos , Cicloexanonas , Doenças das Plantas/microbiologia , Fungos , PlantasRESUMO
Macrophages are critical in both tissue homeostasis and inflammation, and shifts in their polarization have been indicated as pivotal for the resolution of inflammatory processes. Inflammation is a complex and necessary component of the immune response to stimuli that are harmful to host homeostasis and is regulated by cellular and molecular events that remain a source of ongoing investigation. Among the compounds studied that have potential against autoimmune and inflammatory diseases, cannabinoids are currently highlighted. In this work, nineteen aryl-cyclohexanones diesters and their derivatives were synthesized based on the aryl-cyclohexane skeleton of phytocannabinoids, such as cannabidiol (CBD), and were evaluated for their anti-inflammatory and macrophage polarization potential. The results showed that Compound 4 inhibited the production of nitric oxide in RAW 264.7 macrophages. Furthermore, it reduced the levels of pro-inflammatory cytokines IL-12p70, TNF-α, IFN-γ, MCP-1, and IL-6 while, at the same time, was able to increase the production of anti-inflammatory cytokines IL-4, IL-10, and IL-13. Compound 4 also reduced macrophage apoptosis, increased the expression of the CD206 (mannose receptor) and at the same time, decreased the expression of CD284 (TLR-4 receptor) on the surface of these cells. Finally, it increased the phagocytic capacity and inhibited the phosphorylation of the p65 of NF-kß. In conclusion, Compound 4, identified as diethyl-4-hydroxy-2-(4-methoxyphenyl)-4-methyl-6-oxocyclohexane-1-3-dicarboxylate, showed significant anti-inflammatory effect, while demonstrating the ability to transform phenotypically macrophages from the M1 phenotype (pro-inflammatory) to the M2 phenotype (anti-inflammatory). This led us to hypothesize that the main mechanism of anti-inflammatory effect of this molecule is linked to its immune modulation capacity.
Assuntos
Cicloexanonas , Macrófagos , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Cicloexanonas/metabolismo , Cicloexanonas/farmacologia , Citocinas/metabolismo , Humanos , Inflamação/metabolismo , Macrófagos/metabolismoRESUMO
The preparation of a new non-natural gabosine is reported, in which the chirality is transferred from the toluene's biotransformed metabolite (1R,2S)-3-methylcyclohexa-3.5-diene-1,2-diol. Further chemical transformations to introduce additional functionality and chirality to the molecule were also accomplished.
Assuntos
Cicloexanonas/síntese química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populations of insect pollinator species. Here we present a promising, environment-friendly alternative to current insecticides that targets the insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded and eliminated. RNA interference (RNAi) of either the first two enzymes in the tyrosine degradation pathway (tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, oral administration of NTBC to bumblebees did not affect their survival. Using a novel mathematical model, we show that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current disease elimination programmes.
Assuntos
Cicloexanonas/uso terapêutico , Reposicionamento de Medicamentos , Controle de Infecções/métodos , Nitrobenzoatos/uso terapêutico , Tripanossomíase Africana/prevenção & controle , 4-Hidroxifenilpiruvato Dioxigenase/antagonistas & inibidores , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Animais , Abelhas/efeitos dos fármacos , Feminino , Humanos , Inseticidas/uso terapêutico , Masculino , Metaboloma/efeitos dos fármacos , Camundongos , Modelos Teóricos , Doenças Negligenciadas/prevenção & controle , Produção de Droga sem Interesse Comercial , Ratos , Ratos Wistar , Testes de Toxicidade , Tripanossomíase Africana/transmissão , Moscas Tsé-Tsé/efeitos dos fármacos , Moscas Tsé-Tsé/metabolismo , Tirosina/metabolismoRESUMO
The large-scale use of herbicides deteriorates water quality and threatens aquatic biodiversity. Unfortunately, there are few studies on the ecological effects of herbicides on toxin-producing strains of cyanobacteria under changing nutrient conditions. The objective of the present study was to investigate the effects of the herbicide clethodim and nitrogen variation on the allelopathic interactions and toxin production of Microcystis aeruginosa BCCUSP232 and Raphidiopsis raciborskii (formerly known as Cylindrospermopsis raciborskii) ITEPA1. M. aeruginosa had increased cell density when exposed to the clethodim (H +) (23.55 mg/L), whereas the highest cell density of R. raciborskii was observed in the treatment with clethodim plus limited nitrogen. Also, the cell-free exudate of R. raciborskii significantly stimulated the growth of M. aeruginosa on day 3 of the experiment. The concentration of chlorophyll-a in M. aeruginosa cultures generally increased in all the treatments, while in R. raciborskii cultures, the opposite occurred. Total microcystins (MCs) content of M. aeruginosa in the mixed cultures was 68% higher in nitrogen-enriched conditions than the control. A similar increase in MC content occurred in M. aeruginosa unialgal culture treated with R. raciborskii exudate. Total saxitoxin concentration was 81% higher in mixed cultures of R. raciborskii simultaneously exposed to high nitrogen and clethodim. Similarly, unialgal cultures of R. raciborskii exposed to either high nitrogen or clethodim had higher saxitoxins concentrations than the control. The intracellular H2O2 content of M. aeruginosa cultures decreased, whereas, in R. raciborskii cultures, it increased during exposure to high nitrogen and clethodim. Only R. raciborskii had a significant variation in peroxidase activity. The activities of glutathione S-transferase of both strains were higher in the presence of clethodim. These results revealed that nitrogen enrichment and the presence of clethodim might lead to the excessive proliferation of M. aeruginosa and R. raciborskii and increased production of cyanotoxins in aquatic environments.
Assuntos
Cylindrospermopsis , Herbicidas , Microcystis , Cicloexanonas , Peróxido de Hidrogênio , NitrogênioRESUMO
Selaginella convoluta is a desiccation tolerant plant native to the Brazilian semiarid region (Caatinga), endowed with an effective drought resistance mechanism. As part of our research efforts to understand the chemical diversity of S. convoluta, dehydrated (harvested in their natural habitat in the dry season) and hydrated (plant acclimated in a laboratory after rehydration) specimens were analyzed by HR-LC-ESI-MS/MS followed by a structural annotation on the Global Natural Products Social Molecular Networking Web platform. The molecular networking approach allowed for putative annotation of 39 metabolites, mainly selaginellins and flavonoids. Based on MS/MS data, three unprecedented selaginellins were annotated: 29-hydroxy selaginellin O, 29-hydroxy selaginellin A, and 4-{[2-(4-hydrophenyl)-6-[2-(4-hydroxyphenyl)ethynyl]phenyl](4-oxocyclohexa-2,5-dien-1-ylidene)methyl}benzaldehyde. Th results pointed out that valuable scientific knowledge can be obtained from studies conducted with plants in their natural habitat by allowing a more realistic profile of chemical diversity. The present study adds new information on specialized metabolites of S. convoluta, mainly flavonoids and selaginellins, and highlights the species as an untapped source of chemobiodiversity from Caatinga.
Assuntos
Selaginellaceae , Compostos de Bifenilo , Brasil , Cicloexanonas , Flavonoides , Estrutura Molecular , Espectrometria de Massas em TandemRESUMO
In the present study a series of 34 synthetic ligustrazine-containing α, ß-Unsaturated carbonyl-based compounds and oximes, recognized as anticancer compounds were assessed against protozoa of the Trypanosoma and Leishmania species. Ligustrazine, chemically known as tetramethylpyrazine (TMP), was selected as the core moiety for the synthesis of α, ß-Unsaturated carbonyl-based compounds and these compounds were selected as precursors for the synthesis of new oximes. Some derivates, including 5f and 6i, showed multiple activities against all tested strains. In particular compounds 5f and 8o are the most potent and they are, therefore, potential candidates for trypanosomiasis and leishmaniasis
Assuntos
Oximas/agonistas , Cicloexanonas/agonistas , Trypanosoma/classificação , Tripanossomíase , Leishmaniose , Leishmania/classificaçãoRESUMO
Banisteriopsis argyrophylla belongs to the Malpighiaceae family, which is a species from Cerrado, also known as "cipó-prata" or "cipó-folha-de-prata." Several species of this family present biological potential. This work reports the chemical identification of the ethanol extract (EE) and its fractions from B. argyrophylla leaves and shows the analysis of the antioxidant activity and inhibitory effects on activities of α-amylase, α-glucosidase and lipase, and non-enzymatic glycation. The ethyl acetate fraction (EAF) and n-butanol fraction (BF) showed antioxidant activity, with IC50 values of 4.1 ± 0.1 and 4.8 ± 0.1 µg mL-1, respectively, by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and IC50 values of 6046.3 ± 174.2 and 6264.2 ± 32.2 µmol Trolox eq g-1 by the oxygen radical absorbance capacity (ORAC) method. Furthermore, the DPPH method with these fractions presented electroactive species with antioxidant potential, as shown by the differential pulse voltammetry (DPV) method. The inhibitory effects of the EAF and BF were demonstrated by the following results: IC50 of 5.1 ± 0.3 and 2.5 ± 0.2 µg mL-1 for α-amylase, IC50 of 1093.5 ± 26.0 and 1250.8 ± 21.9 µg mL-1 for α-glucosidase, IC50 of 8.3 ± 4.1 and 4.4 ± 1.0 µg mL-1 for lipase, and IC50 of 1.3 ± 0.1 and 0.9 ± 0.1 µg mL-1 for glycation. Some bioactive compounds were identified by (-)-ESI-MS/MS, such as catechin, procyanidins, glycosylated flavonoids, kaempferol, and megastigmane glucosides. The antidiabetic activity of B.argyrophylla has been reported for the first time.
Assuntos
Antioxidantes/química , Banisteriopsis/química , Inibidores Enzimáticos/química , Extratos Vegetais/química , Folhas de Planta/química , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Antioxidantes/farmacologia , Catequina/química , Catequina/farmacologia , Cicloexanonas/química , Cicloexanonas/farmacologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Glicosilação , Humanos , Hipoglicemiantes/química , Quempferóis/química , Quempferóis/farmacologia , Lipase/metabolismo , Norisoprenoides/química , Norisoprenoides/farmacologia , Extratos Vegetais/farmacologia , Proantocianidinas/química , Proantocianidinas/farmacologiaRESUMO
The self-assembly of model [P]RWG lipopeptides (P: l-proline, R: l-arginine, W: l-tryptophan, G: l-glycine), containing one or two aliphatic octadecyl (C18) chains in water and cyclohexanone/water solutions was examined. The self-assembly of mixtures of these RWG and PRWG lipopeptides was also investigated. These materials presented a similar critical aggregation concentration of â¼4.0 × 10-4 wt% and were characterized by unordered secondary structures with some ß-sheet content. TEM and cryo-TEM revealed the presence of mainly nanotape structures with micelles observed for systems rich in PRWG(C18H37). Analysis of detailed SAXS form factor measurements revealed the presence of bilayers 3-4 nm thick while the PRWG(C18H37) micelles have a core radius of approximately 3 nm, and a shell thickness of 2 nm. For the cyclohexanone/water systems polymorphs containing cluster aggregates (with radius of 0.25 nm to 0.50 nm) and some elongated structures (with radius of 5.7 nm to 26.1 nm) were seen. Longer structures were formed with the increase of the proline-containing lipopeptide content. The catalytic activity of these peptides was assessed using a model nitro-aldol reaction. The concentration of water in the reaction system influenced the conversion, higher content promoted better efficiency for the water systems, but the opposite was observed for the cyclohexanone/water samples.