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The importance of essential oils and their components in the industrial sector is attributed to their chemical characteristics and their application in the development of products in the areas of cosmetology, food, and pharmaceuticals. However, the pharmacological properties of this class of natural products have been extensively investigated and indicate their applicability for obtaining new drugs. Therefore, this review discusses the use of these oils as starting materials to synthesize more complex molecules and products with greater commercial value and clinic potential. Furthermore, the antiulcer, cardiovascular, and antidiabetic mechanisms of action are discussed. The main mechanistic aspects of the chemopreventive properties of oils against cancer are also presented. The data highlight essential oils and their derivatives as a strategic chemical group in the search for effective therapeutic agents against various diseases.
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Phytol is a diterpene constituent of many essential oils, belonging to the group of unsaturated acyclic alcohols. Although phytol possesses antimycobacterial and anti-inflammatory effects, no reports of a gastrointestinal action are available from the literature. Due to the well-known shortcomings of classical anti-ulcer drugs (e.g. side effects or relapses), natural products may offer an attractive alternative. In this study, a potential gastroprotective activity of phytol was evaluated using acute and chronic ulcer models in rats. Phytol 12.5, 25 and 50 mg/kg, administered orally 1 h prior to induction of gastric lesions by absolute ethanol, inhibited the lesion area by 96, 90 and 95%, respectively. When lesions were induced by ischemia and reperfusion, phytol 12.5 and 25 mg/kg per os decreased the lesion areas by 89 and 46%, respectively. In the third acute ulcer model (lesions induced by ibuprofen), phytol 12.5 mg/kg reduced the lesion area by 55%. Phytol restored the decreased level of reduced glutathione, the increased levels of myeloperoxidase and malondialdehyde and the decreased levels of catalase and superoxide dismutase in rats with gastric ulcer induced by ethanol to levels obtained in vehicle group. Finally, in a chronic model in which gastric ulcer was induced by acetic acid directly instilled into the stomach, phytol administered orally over a time period of 7 days at 12.5, 25, 50 and 100 mg/kg reduced lesion areas by 84, 81, 83 and 68%. Our data suggest a gastroprotective and cicatrizing effect of phytol, possibly associated with its antioxidant effect.
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Antiulcerosos , Modelos Animais de Doenças , Etanol , Fitol , Ratos Wistar , Úlcera Gástrica , Animais , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Masculino , Fitol/farmacologia , Fitol/uso terapêutico , Ratos , Glutationa/metabolismo , Malondialdeído/metabolismo , Catalase/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Superóxido Dismutase/metabolismo , Ibuprofeno/farmacologia , Ibuprofeno/uso terapêutico , Peroxidase/metabolismo , Antioxidantes/farmacologiaRESUMO
The objective of this study was to evaluate the antifungal activity of free methyl 3,5 dinitrobenzoate (MDNB) and its nanoemulsion (MDNB-NE) against strains of Candida albicans. Additionally, a molecular modeling study was also carried out to propose the mechanism of action and toxicity of MDNB. These results demonstrated the MDNB-NE presented a droplet size of 181.16 ± 3.20 nm and polydispersity index of 0.30 ± 0.03. MDNB and MDNB-NE inhibited the growth of all strains with minimum inhibitory concentrations of 0.27-1.10 mM. The biological results corroborated the molecular model, which pointed to a multi-target antifungal mechanism of action for MDNB in C. albicans. The study could serve as a basis for further research involving compounds with nitro groups with antifungal.
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Antifúngicos , Candida albicans , Nitrobenzoatos , Antifúngicos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
The acute toxicity and hypokinetic activity induced by menthofuran on the gastrointestinal tract of rodents were investigated in the present study. An absence of acute toxicity was observed. Menthofuran delayed gastric emptying at oral doses of 25, 50, and 100 mg/kg in the experimental model of phenol red, as well as it reduced the intestinal transit at oral doses of 50 and 100 mg/kg. Interestingly, a scopolamine-similar hypokinetic effect was observed for menthofuran. In the experimental model of castor oil-induced intestinal hypermotility, menthofuran (50 and 100 mg/kg) reduced the number of loose stools as observed for the normal group. Additionally, menthofuran induced a marked concentration-dependent relaxation in rat ileum segments precontracted with KCl (EC50 = 0.059 ± 0.008 µg/mL) or carbachol (EC50 = 0.068 ± 0.007 µg/mL). These results suggest the possible decrease of calcium influx underlying the effects of menthofuran on the gastrointestinal tract, which opens the door for further study regarding this potential application for the treatment of gastrointestinal disorders, noting possible limitations of its use due to adverse effects in children.
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Menthofuran is a monoterpene present in various essential oils derived from species from Mentha genus, and in Brazil, those species are widely used in treating gastrointestinal and respiratory disorders. Considering the wide pharmacological potential of monoterpenes, including their antioxidant activity, this study aimed to evaluate menthofuran-gastroprotective activity, as well as the involvement of antioxidant mechanisms in this effect. The acute toxicity was evaluated according to the fixed dose method. The antiulcerogenic activity was investigated by using experimental models of gastric ulcers induced by ethanol, indomethacin, and ischemia/reperfusion in rats. The antisecretory gastric activity, the catalase activity, and the gastric wall mucus were determined in pylorus ligated rats. Gastric wall nonprotein sulfhydryl (NPSH) group content, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) content were evaluated in ethanol-induced the gastric ulcer model. Menthofuran (2 g/kg) presented low acute toxicity and showed gastroprotective activity against ethanol-, indomethacin-, and ischemia/reperfusion-induced ulcers. Moreover, menthofuran presented antisecretory activity, reduced the total acidity, and increased pH of gastric secretion. On the other hand, a decrease in mucus content of gastric wall without alteration of gastric juice volume and catalase activity was observed. Interestingly, menthofuran increased NPSH levels and reduced MDA levels and MPO activity. Gastroprotective effects of menthofuran appear to be mediated, at least in part, by the NOS pathway, endogenous prostaglandins, reduced gastric juice acidity, increased concentration of the NPSH groups, and reduced lipidic peroxidation. These findings support the menthofuran as an effective gastroprotective agent, as well as the marked participation of antioxidant mechanisms in this response.
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Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) in South America, the Mediterranean basin, and West and Central Asia. The most affected country, Brazil, reported 4297 VL cases in 2017. L. infantum is transmitted by female phlebotomine sand flies during successive blood meals. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new antileishmanial drugs. Cinnamic acid derivatives have shown several pharmacological activities, including antiparasitic action. Therefore, in the present study, the biological evaluation of cinnamic acid and thirty-four derivatives against L. infantum is reported. The compounds were prepared by several synthesis methods and characterized by spectroscopic techniques and high-resolution mass spectrometry. The results revealed that compound 32 (N-(4-isopropylbenzyl)cinnamamide) was the most potent antileishmanial agent (IC50 = 33.71 µM) with the highest selectivity index (SI > 42.46), followed by compound 15 (piperonyl cinnamate) with an IC50 = 42.80 µM and SI > 32.86. Compound 32 was slightly less potent and nineteen times more selective for the parasite than amphotericin B (MIC = 3.14 uM; SI = 2.24). In the molecular docking study, the most likely target for the compound in L. infantum was aspartyl aminopeptidase, followed by aldehyde dehydrogenase, mitochondrial. The data obtained show the antileishmanial potential of this class of compounds and may be used in the search for new drug candidates against Leishmania species.
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Antiprotozoários , Leishmania infantum , Leishmaniose Visceral , Feminino , Humanos , Simulação de Acoplamento Molecular , Antiprotozoários/química , Leishmaniose Visceral/tratamento farmacológico , Cinamatos/farmacologia , Cinamatos/uso terapêutico , BrasilRESUMO
An intense effort has been focused on new therapeutic approaches and the development of technologies for more efficient and rapid wound healing. The research for plants used for long time in traditional medicine in the treatment of wound has become a promising strategy to obtain drugs therapeutically useful in the acute and chronic wound management. In this context, Centella asiatica (Apiaceae) has been used to treat a variety of skin diseases, such as leprosy, lupus, varicose ulcers, eczema and psoriasis, in Asiatic traditional medicine for thousands of years. Studies have shown that Centella asiatica extracts (CAE) display activity in tissue regeneration, cell migration and wound repair process by promoting fibroblast proliferation and collagen synthesis. Preliminary findings have shown that the asiatic acid is one of the main active constituents of C. asiatica, directly associated with its healing activity. Thus, this study discusses aspects of the effects of Centella asiatica and its active component, asiatic acid, in different stages of the healing process of cutaneous wounds, including phytochemical and antimicrobial aspects that contribute to its therapeutic potential.
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The severity of infectious diseases associated with the resistance of microorganisms to drugs highlights the importance of investigating bioactive compounds with antimicrobial potential. Therefore, nineteen synthetic cinnamides and cinnamates having a cinnamoyl nucleus were prepared and submitted for the evaluation of antimicrobial activity against pathogenic fungi and bacteria in this study. To determine the minimum inhibitory concentration (MIC) of the compounds, possible mechanisms of antifungal action, and synergistic effects, microdilution testing in broth was used. The structures of the synthesized products were characterized with FTIR spectroscopy, 1 H-NMR, 13 C-NMR, and HRMS. Derivative 6 presented the best antifungal profile, suggesting that the presence of the butyl substituent potentiates its biological response (MIC = 626.62 µM), followed by compound 4 (672.83 µM) and compound 3 (726.36 µM). All three compounds were fungicidal, with MFC/MIC ≤ 4. For mechanism of action, compounds 4 and 6 directly interacted with the ergosterol present in the fungal plasmatic membrane and with the cell wall. Compound 18 presented the best antibacterial profile (MIC = 458.15 µM), followed by compound 9 (550.96 µM) and compound 6 (626.62 µM), which suggested that the presence of an isopropyl group is important for antibacterial activity. The compounds were bactericidal, with MBC/MIC ≤ 4. Association tests were performed using the Checkerboard method to evaluate potential synergistic effects with nystatin (fungi) and amoxicillin (bacteria). Derivatives 6 and 18 presented additive effects. Molecular docking simulations suggested that the most likely targets of compound 6 in C. albicans were caHOS2 and caRPD3, while the most likely target of compound 18 in S. aureus was saFABH. Our results suggest that these compounds could be used as prototypes to obtain new antimicrobial drugs.
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Anti-Infecciosos , Antifúngicos , Antifúngicos/farmacologia , Staphylococcus aureus , Cinamatos/farmacologia , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Candida albicans , Testes de Sensibilidade MicrobianaRESUMO
Acute kidney injury (AKI) has been increasingly reported in critically-ill COVID-19 patients. Moreover, there was significant positive correlation between COVID-19 deaths and renal disorders in hospitalized COVID-19 patients with underlying comorbidities who required renal replacement therapy. It has suggested that death in COVID-19 patients with AKI is 3-fold higher than in COVID-19 patients without AKI. The pathophysiology of COVID-19-associated AKI could be attributed to unspecific mechanisms, as well as COVID-19-specific mechanisms such as direct cellular injury, an imbalanced renin-angiotensin-aldosterone system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. To date, there is no specific treatment for COVID-19 and its associated AKI. Luteolin is a natural compound with multiple pharmacological activities, including anticoronavirus, as well as renoprotective activities against kidney injury induced by sepsis, renal ischemia and diverse nephrotoxic agents. Therefore, in this review, we mechanistically discuss the anti-SARS-CoV-2 and renoprotective activities of luteolin, which highlight its therapeutic potential in COVID-19-AKI patients.
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Injúria Renal Aguda , Tratamento Farmacológico da COVID-19 , COVID-19 , Humanos , COVID-19/complicações , Luteolina/farmacologia , Luteolina/uso terapêutico , SARS-CoV-2 , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Estado TerminalRESUMO
Hemorrhagic cystitis is the main adverse effect associated with the clinical use of oxazaphosphorine, resulting in increased oxidative stress and proinflammatory cytokines, which culminate in injury of the bladder tissue. The aim of this study was to evaluate the protective effect of isopropyl gallate (IPG) against ifosfamide (IFOS)-induced hemorrhagic cystitis in mice. The induction of the hemorrhagic cystitis model was carried out using a single dose of IFOS (400 mg/kg, i.p.) four hours after oral pretreatment with IPG (6.25, 12.5, 25, and 50 mg/kg) or saline (vehicle). Mesna (positive control; 80 mg/kg, i.p.) was administered four hours before and eight hours after induction of cystitis. In the present study, IPG 25 mg/kg significantly decreased edema and hemorrhage, with a reduction of the bladder wet weight (36.86%), hemoglobin content (54.55%), and peritoneal vascular permeability (42.94%) in urinary bladders of mice. Interestingly, IPG increased SOD activity (89.27%) and reduced MDA levels (35.53%), as well as displayed anti-inflammatory activity by decreasing TNF-α (88.77%), IL-1ß (62.87%), and C-reactive protein (56.41%) levels. Our findings demonstrate that IPG has a substantial protective role against IFOS-induced hemorrhagic cystitis in mice by enhancing antioxidant activity and proinflammatory mechanisms. Thus, IPG represents a promising co-adjuvant agent in oxazaphosphorine-based chemotherapy treatments.
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By submitting this manuscript, each author certifies that they have made a direct and substantial contribution to the work reported in the manuscript. In this manuscript the conception, design, investigation, acquisition of data and analysis, interpretation of data and writing of the article were conducted by author Camila Bomfim de Sá under the guidance of professors Margareth de Fátima Formiga Melo Diniz, Hilzeth de Luna Freire Pessôa and Caliandra Maria Bezerra Luna Lima, who also approved the final version of the manuscript. Professor Damião Pergentino de Sousa and his student Mayara Castro de Morais performed the production, synthesis and chemical characterization of ethyl ferulate (EF). Professor Abrahão Alves de Oliveira Filho assessed the in silico tests. PhD student Andressa Brito Lira participated in the critical review of the text for important intellectual content and assisted in the in vitro antioxidant activity and cytotoxicity tests. Kardilandia Mendes de Oliveira participated in acute oral toxicity tests evaluating the biochemical parameters. Students, Tafaela Dias and Cinthia Rodrigues Melo also assisted in the acute oral toxicity testing and preparing of slides for histopathological analysis. Pathologist Alexandre Rolim da Paz analyzed the histopathology results. EF, a phenolic compound of the large class of phenylpropanoids, is derived from ferulic acid and is produced both naturally and synthetically. Its principal pharmacological activities are: anti-inflammatory and antioxidant activity. This study aimed to investigate the in silico, in vitro and in vivo toxicity and antioxidant activity of EF. The in silico prediction showed more than 20 biological activities as well as good absorption at the biological membranes and no theoretical toxicity. However, EF presented high environmental toxicity. EF presented low hemolytic potential and exerted protective activity for the erythrocyte membrane for only blood type O. EF presented antioxidant activity against H2O2 at all concentrations and all blood types, but no effect against phenylhydrazine, being unable to prevent its oxidative effects. In the acute nonclinical toxicological trial, the treated animals presented behavioral changes (e.g., sedation). Feed intake was higher for the 2000 mg/kg group, but with no significant difference in weight change. The biochemical parameters presented no differences between treated and control animals, and the organs remained intact with no change. Thus, EF presents a low toxic profile and this study provides important information about the toxicity of this compound, suggesting future safe use.
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Antioxidantes , Peróxido de Hidrogênio , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Ácidos Cafeicos/química , Humanos , OxirreduçãoRESUMO
Amides derived from ferulic acid have a wide spectrum of pharmacological activities, including antitumor and antifungal activity. In the present study, a series of ten amides were obtained by coupling reactions using the reagents (benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate (PyBOP) and N,N'-dicyclohexylcarbodiimide (DCC). All the compounds were identified on the basis of their IR, 1H- and 13C-NMR, HRMS data, and with yields ranging from 43.17% to 91.37%. The compounds were subjected to cytotoxic tests by the alamar blue technique and antifungal screening by the broth microdilution method to determine the minimum inhibitory concentration (MIC). The amides 10 and 11 displayed the best result in both biological evaluations, and compound 10 was the most potent and selective in HL-60 cancer cells, with no cytotoxicity on healthy cells. This amide had antifungal activity in all strains and had the lowest MIC against Candida albicans and Candida tropicalis. The possible mechanism of antifungal action occurs via the fungal cell wall. Molecular modeling suggested that compounds 10 and 11 interact with the enzymes GWT1 and GSC1, which are essential for the development of C. albicans. The findings of the present study demonstrated that compounds 10 and 11 may be used as a platform in drug development in the future.
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Ácidos Cumáricos/farmacologia , Dicicloexilcarbodi-Imida/química , Compostos Organofosforados/química , Triazóis/química , Amidas/química , Amidas/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Ácidos Cumáricos/química , Dicicloexilcarbodi-Imida/farmacologia , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Óleos Voláteis/química , Compostos Organofosforados/farmacologia , Triazóis/farmacologiaRESUMO
Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5-46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.
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Injúria Renal Aguda/etiologia , Antivirais/farmacologia , COVID-19/complicações , Catequina/farmacologia , Substâncias Protetoras/farmacologia , Injúria Renal Aguda/tratamento farmacológico , Animais , Antivirais/química , Antivirais/uso terapêutico , Catequina/química , Catequina/uso terapêutico , Humanos , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The disease has been associated with high mortality rate, especially in patients with comorbidities such as diabetes, cardiovascular and kidney diseases. This could be attributed to dysregulated immune responses and severe systemic inflammation in COVID-19 patients. The use of effective antiviral drugs against SARS-CoV-2 and modulation of the immune responses could be a potential therapeutic strategy for COVID-19. Studies have shown that natural phenolic compounds have several pharmacological properties, including anticoronavirus and immunomodulatory activities. Therefore, this review discusses the dual action of these natural products from the perspective of applicability at COVID-19.
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Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Flavonoides/uso terapêutico , Fatores Imunológicos/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Inibidores de Proteases/uso terapêutico , Animais , Antivirais/química , Antivirais/farmacologia , Coronavirus/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologiaRESUMO
INTRODUCTION: The absence of a standardized classification scheme for the antifungal potency of compounds screened against Candida species may hinder the study of new drugs. This systematic review proposes a scheme of interpretative breakpoints for the minimum inhibitory concentration (MIC) of bioactive compounds against Candida species in in vitro tests. MATERIALS AND METHODS: A literature search was conducted in the PubMed, Scopus, Web of Science, Lilacs, and SciFinder databases for the period from January 2015 to April 2020. The following inclusion criterion was used: organic compounds tested by the microdilution technique according to the Clinical and Laboratory Standards Institute protocol against reference strains of the genus Candida. A total of 545 articles were retrieved after removing duplicates. Of these, 106 articles were selected after applying the exclusion criteria and were evaluated according to the number of synthesized molecules and their chemical classes, the type of strain (reference or clinical) used in the antifungal test, the Candida species, and the MIC (in µg/mL) used. RESULTS: The analysis was performed based on the median, quartiles (25% and 75%), maximum, and minimum values of four groups: all strains, ATCC strains, C. albicans strains, and C. albicans ATCC strains. The following breakpoints were proposed to define the categories: MIC < 3.515 µg/mL (very strong bioactivity); 3.516-25 µg/mL (strong bioactivity); 26-100 µg/mL (moderate bioactivity); 101-500 µg/mL (weak bioactivity); 500-2000 µg/mL (very weak bioactivity); and >2000 µg/mL (no bioactivity). CONCLUSIONS: A classification scheme of the antifungal potency of compounds against Candida species is proposed that can be used to identify the antifungal potential of new drug candidates.
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Antifúngicos/análise , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Bibliometria , Humanos , Testes de Sensibilidade MicrobianaRESUMO
The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus; the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Millions of cases and deaths to date have resulted in a global challenge for healthcare systems. COVID-19 has a high mortality rate, especially in elderly individuals with pre-existing chronic comorbidities. There are currently no effective therapeutic approaches for the prevention and treatment of COVID-19. Therefore, the identification of effective therapeutics is a necessity. Terpenes are the largest class of natural products that could serve as a source of new drugs or as prototypes for the development of effective pharmacotherapeutic agents. In the present study, we discuss the antiviral activity of these natural products and we perform simulations against the Mpro and PLpro enzymes of SARS-CoV-2. Our results strongly suggest the potential of these compounds against human coronaviruses, including SARS-CoV-2.
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Antivirais/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Descoberta de Drogas , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Terpenos/farmacologia , Antivirais/química , COVID-19/virologia , Proteases 3C de Coronavírus/metabolismo , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , SARS-CoV-2/enzimologia , Terpenos/química , Tratamento Farmacológico da COVID-19RESUMO
Bioactive compounds found in food and medicinal plants contribute to maintaining health and treating illnesses. For example, hydroxycinnamic acids, such as ferulic acid, are widely present in nature and have several pharmacological properties, including antioxidant, anti-inflammatory, and beneficial effects in parameters of diabetes and hyperlipidemia. The results of studies in animal models and in vitro experiments of ferulic acid suggest its high therapeutic and preventive potential against several pathological disorders, such as cardiovascular diseases. Therefore, in this review, the bioactivities of ferulic acid on the cardiovascular system are described, including the discussion of the mechanisms of action in the various components of the system. In this review, we discuss the pharmacological properties of this versatile natural product in aspects of cardiovascular health, including cardioprotective and antihypertensive actions, and on the metabolism of lipids, diabetes, and thrombosis.
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Doenças Cardiovasculares/prevenção & controle , Ácidos Cumáricos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Trombose/tratamento farmacológico , Vasodilatação/efeitos dos fármacosRESUMO
Fungal infections remain a high-incidence worldwide health problem that is aggravated by limited therapeutic options and the emergence of drug-resistant strains. Cinnamic and benzoic acid amides have previously shown bioactivity against different species belonging to the Candida genus. Here, 20 cinnamic and benzoic acid amides were synthesized and tested for inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019. Five compounds inhibited the Candida strains tested, with compound 16 (MIC = 7.8 µg/mL) producing stronger antifungal activity than fluconazole (MIC = 16 µg/mL) against C. krusei ATCC 14243. It was also tested against eight Candida strains, including five clinical strains resistant to fluconazole, and showed an inhibitory effect against all strains tested (MIC = 85.3-341.3 µg/mL). The MIC value against C. krusei ATCC 6258 was 85.3 mcg/mL, while against C. krusei ATCC 14243, it was 10.9 times smaller. This strain had greater sensitivity to the antifungal action of compound 16. The inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019 was also achieved by compounds 2, 9, 12, 14 and 15. Computational experiments combining target fishing, molecular docking and molecular dynamics simulations were performed to study the potential mechanism of action of compound 16 against C. krusei. From these, a multi-target mechanism of action is proposed for this compound that involves proteins related to critical cellular processes such as the redox balance, kinases-mediated signaling, protein folding and cell wall synthesis. The modeling results might guide future experiments focusing on the wet-lab investigation of the mechanism of action of this series of compounds, as well as on the optimization of their inhibitory potency.
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Amidas/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Modelos Moleculares , Amidas/química , Anti-Infecciosos/farmacologia , Halogenação , Testes de Sensibilidade Microbiana , TermodinâmicaRESUMO
The outbreaks of viruses with wide spread and mortality in the world population have motivated the research for new therapeutic approaches. There are several viruses that cause a biochemical imbalance in the infected cell resulting in oxidative stress. These effects may be associated with the development of pathologies and worsening of symptoms. Therefore, this review is aimed at discussing natural compounds with both antioxidant and antiviral activities, specifically against coronavirus infection, in an attempt to contribute to global researches for discovering effective therapeutic agents in the treatment of coronavirus infection and its severe clinical complications. The contribution of the possible action of these compounds on metabolic modulation associated with antiviral properties, in addition to other mechanisms of action, is presented.
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Antioxidantes/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Coronavirus/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Coronavirus/patogenicidade , Infecções por Coronavirus/virologia , HumanosRESUMO
Ethyl ferulate, a phenylpropanoid derived from rice hulls has aroused interest because of its antioxidant, anti-inflammatory and neuroprotective properties. However, it has low solubility in water which compromises the absorption in the gastrointestinal tract, decreases the bioavailability and compromises the reproducibility of the effects in vivo. To increase the solubility of ethyl ferulate, inclusion complexes were obtained by physical mixing, malaxing, lyophilization and spray drying and characterized using thermal analysis, XRD and FTIR. The complexes obtained were evaluated for ethyl ferulate content, stability, dissolution profile and evaluation of anti-inflammatory activity in vivo through carrageenan-induced paw edema model in rats. The inclusion complexes obtained resulted in increased solubility and stability compared to the isolated ethyl ferulate. In addition, the complexes obtained by malaxage, lyophilization and spray drying showed greater inhibition of the edema formation induced by carrageenan compared to ethyl ferulate 100 mg/kg v.o. The inclusion of ethyl ferulate in B-cyclodextrin resulted in the formation of stable inclusion complexes with potent antidematogenic activity possibly attributed to the increased solubility, dissolution profile of the active.