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1.
Plant Physiol Biochem ; 204: 108127, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37890229

RESUMO

Enzymes of the sulfur assimilation pathway of plants have been identified as potential targets for herbicide development, given their crucial role in synthesizing amino acids, coenzymes, and various sulfated compounds. In this pathway, O-acetylserine (thiol) lyase (OAS-TL; EC 2.5.1.47) catalyzes the synthesis of L-cysteine through the incorporation of sulfate into O-acetylserine (OAS). This study used an in silico approach to select seven inhibitors for OAS-TL. The in silico experiments revealed that S-benzyl-L-cysteine (SBC) had a better docking score (-7.0 kcal mol-1) than the substrate OAS (-6.6 kcal mol-1), indicating its suitable interaction with the active site of the enzyme. In vitro experiments showed that SBC is a non-competitive inhibitor of OAS-TL from Arabidopsis thaliana expressed heterologously in Escherichia coli, with a Kic of 4.29 mM and a Kiu of 5.12 mM. When added to the nutrient solution, SBC inhibited the growth of maize and morning glory weed plants due to the reduction of L-cysteine synthesis. Remarkably, morning glory was more sensitive than maize. As proof of its mechanism of action, L-cysteine supplementation to the nutrient solution mitigated the inhibitory effect of SBC on the growth of morning glory. Taken together, our data suggest that reduced L-cysteine synthesis is the primary cause of growth inhibition in maize and morning glory plants exposed to SBC. Furthermore, our findings indicate that inhibiting OAS-TL could potentially be a novel approach for herbicidal action.


Assuntos
Arabidopsis , Herbicidas , Liases , Arabidopsis/metabolismo , Cisteína , Cisteína Sintase/metabolismo , Herbicidas/farmacologia , Plantas/metabolismo , Compostos de Sulfidrila/metabolismo
2.
J Biomol Struct Dyn ; 41(21): 12204-12213, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36651196

RESUMO

The deaths caused by the covid-19 pandemic have recently decreased due to a worldwide effort in vaccination campaigns. However, even vaccinated people can develop a severe form of the disease that requires ICU admission. As a result, the search for antiviral drugs to treat these severe cases has become a necessity. In this context, natural products are an interesting alternative to synthetic medicines used in drug repositioning, as they have been consumed for a long time through traditional medicine. Many natural compounds found in plant extracts have already been shown to be effective in treating viral and bacterial diseases, making them possible hits to exploit against covid-19. The objective of this work was to evaluate the antiviral activity of different plant extracts available in the library of natural products of the Universidade Estadual de Maringá, by inhibiting the SARS-CoV-2 main protease (Mpro), and by preventing viral infection in a cellular model. As a result, the extract of Cytinus hypocistis, obtained by ultrasound, showed a Mpro inhibition capacity greater than 90%. In the infection model assays using Vero cells, an inhibition of 99.6% was observed, with a selectivity index of 42.7. The in silico molecular docking simulations using the extract compounds against Mpro, suggested Tellimagrandin II as the component of C. hypocistis extract most likely to inhibit the viral enzyme. These results demonstrate the potential of C. hypocistis extract as a promising source of natural compounds with antiviral activity against covid-19.Communicated by Ramaswamy H. Sarma.


Assuntos
Produtos Biológicos , COVID-19 , Humanos , Chlorocebus aethiops , Animais , Simulação de Acoplamento Molecular , Pandemias , SARS-CoV-2 , Células Vero , Extratos Vegetais/farmacologia , Antivirais/farmacologia , Inibidores de Proteases/farmacologia , Simulação de Dinâmica Molecular
3.
J Biomol Struct Dyn ; 41(15): 7297-7308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36069130

RESUMO

Few extracts of plant species from the Brazilian flora have been validated from a pharmacological and clinical point of view, and it is important to determine whether their traditional use is proven by pharmacological effects. Cenostigma pluviosum var. peltophoroides is one of those plants, which belongs to the Fabaceae family that is widely used in traditional medicine and is very rich in tannins. Due to the lack of effective drugs to treat severe cases of Covid-19, the main protease of SARS-CoV-2 (Mpro) becomes an attractive target in the research for new antivirals since this enzyme is crucial for virus replication and does not have homologs in humans. This study aimed to prospect inhibitor candidates among the compounds from C. pluviosum extract, by virtual screening simulations using SARS-CoV-2 Mpro as target. Experimental validation was made by inhibitory proteolytic assays of recombinant Mpro and by antiviral activity with infected Vero cells. Docking simulations identify four compounds with potential inhibitory activity of Mpro present in the extract. The compound pentagalloylglucose showed the best result in proteolytic kinetics experiments, with suppression of recombinant Mpro activity by approximately 60%. However, in experiments with infected cells ethyl acetate fraction and sub-fractions, F2 and F4 of C. pluviosum extract performed better than pentagalloylglucose, reaching close to 100% of antiviral activity. The prominent activity of the extract fractions in infected cells may be a result of a synergistic effect from the different hydrolyzable tannins present, performing simultaneous action on Mpro and other targets from SARS-CoV-2 and host.Communicated by Ramaswamy H. Sarma.

4.
J Ethnopharmacol ; 295: 115403, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35643209

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves, bark, and roots of Gallesia integrifolia are consumed in folk medicine through infusion, decoction, and topical preparation by crushing because of its pharmacological properties in several peripheral system disorders, including microbial infections. The presence of various molecules in different parts of the plant likely confers this species' fungicidal action, but scientific evidence is lacking. Vulvovaginal candidiasis mainly affects women of reproductive age. When left untreated, it can cause pregnancy complications. Currently available antifungals often cause undesirable side effects. New alternative therapeutic strategies based on medicinal plants have been proposed. AIM: To investigate the antifungal activity of G. integrifolia against vulvovaginal candidiasis secretion in pregnant women. MATERIALS AND METHODS: Antifungal activity was determined by the minimum inhibitory concentration (MIC), determined by broth microdilution method using Candida spp (NEWP1210), C. albicans (CCCD-CC001), C. tropicalis (CCCD-CC002) standard and clinical isolates from pregnant women with vulvovaginal candidiasis. Nystatin and fluconazole were used as positive controls. The chemical composition of essential oils that were extracted from leaves, flowers, and fruits of G. integrifolia was determined by gas chromatography coupled to mass spectrometry. Reverse docking was used to suggest a possible target in Candida. Conventional docking was used to identify the most probable compound that inhibits fungal growth. RESULTS: A total of 24 compounds were identified, accounting for ∼99% of volatile constituents in the essential oils. Leaves of G. integrifolia contained 3,5-dithiahexanol-5,5-dioxide (40.93%), flowers contained methionine ethyl ester (46.78%), and fruits contained 2,8-dithianonane (54.01%) as the most abundant compounds. The MICs of essential oils of leaves, flowers, and fruits of G. integrifolia against standard strains of Candida spp, C. albicans, and C. tropicalis ranged from 13.01 to 625.00 µg/mL. The essential oil of flowers more effectively inhibited Candida spp. Essential oils of leaves and flowers were similar to fluconazole against C. albicans. Essential oils of flowers and fruits were similar to fluconazole against C. tropocalis. In Candida yeast species that were isolated from vaginal secretion samples from pregnant patients, the MICs of leaves and flowers ranged from 52.08 to 5000.00 µg/mL. The essential oil of leaves (277.77 µg/mL) was the most active against C. albicans. No significant differences were found between the essential oils of leaves and flowers against C. glabrata. Docking simulations suggested that phytol in leaves and flowers was responsible for the antimicrobial effect. CONCLUSION: The present results suggest the potential therapeutic use of G. integrifolia, especially its leaves and flowers, against Candida and vulvovaginal candidiasis.


Assuntos
Candidíase Vulvovaginal , Alho , Óleos Voláteis , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candida albicans , Candida glabrata , Candida tropicalis , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Feminino , Fluconazol/farmacologia , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Gravidez , Gestantes
5.
Photochem Photobiol ; 83(6): 1529-36, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18028229

RESUMO

The aim of this work was to apply photoacoustic spectroscopy for the ex vivo determination of the penetration rate of a phytotherapic formulation for vitiligo therapeutic, with or without salicylic acid as the promoter agent. In addition, the compound toxicity and morphophysiology effects were evaluated for different concentrations of salicylic acid. The experiments were performed as a function of the period of time of treatment in a well-controlled group of rabbits. Toxic effects were not observed with any of the tested products. All formulations containing salicylic acid induced cutaneous reaction which was dose dependent. The histological analysis showed that the use of the medication was associated with an increased comedogenic effect in relation to the control group, regardless of salicylic acid concentration. Inflammatory reactions and acanthosis were observed only in the animals treated with formulations containing higher concentrations of salicylic acid, while none of these effects were detected with the use of the formulation containing 2.5% (wt/vol) of salicylic acid. Photoacoustic depth monitoring showed that both formulations, with or without salicylic acid, propagated through the skin up to the melanocytes region, suggesting that the transport of the active agent may occur through the epithelial structure without the need of using queratinolitic substances, which are known to induce side effects in the animals.


Assuntos
Melaninas/metabolismo , Fitoterapia , Absorção Cutânea/efeitos dos fármacos , Vitiligo/tratamento farmacológico , Vitiligo/metabolismo , Animais , Contagem de Leucócitos , Masculino , Coelhos , Vitiligo/patologia
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