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1.
J Ethnopharmacol ; 330: 118200, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38621467

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria eradication has been a major goal of the Indonesian government since 2020. Medicinal plants, such as Strychnos lucida R. Br., are empirically used to treat malaria through traditional preparation methods. However, the safety and efficacy of these plants have not yet been confirmed. Therefore, further investigations are necessary to confirm the safety and efficacy of S. lucida as an antimalarial agent. AIMS OF THE STUDY: To quantify the concentration of brucine in the S. lucida extract, determine the acute oral toxicity of the standardized extract, and evaluate the in vivo antimalarial potency of S. lucida tablet (SLT). MATERIALS AND METHODS: Acute oral toxicity of S.lucida extract was determined using the Organization for Economic Co-operation and Development 420 procedure, and the analytical method for brucine quantification was validated using high-performance liquid chromatography. In addition, antimalarial activity was determined using the Peter's four-day suppressive method. RESULTS: Acute toxicity analysis revealed S. lucida as a low-toxicity compound with a cut-off median lethal dose of 2000-5000 mg/kg body weight [BW], which was supported by the hematological and biochemical profiles of the kidneys, liver, and pancreas (p > 0.05). Extract standardization revealed that S. lucida contained 3.91 ± 0.074% w/w brucine, adhering to the limit specified in the Indonesian Herbal Pharmacopeia. Antimalarial test revealed that SLT inhibited the growth of Plasmodium berghei by 27.74-45.27%. Moreover, SLT improved the hemoglobin and hematocrit levels. White blood cell and lymphocyte counts were lower in the SLT-treated group than in the K (+) group (p < 0.05). CONCLUSION: Histopathological and biochemical evaluations revealed that S. lucida extract was safe at a dose of 2000 mg/kg BW with low toxicity. SLT inhibited Plasmodium growth and improved the hemoglobin, hematocrit, and red blood cell profiles. Additionally, SLT reduced the lymphocyte and WBC counts and increased the monocyte and thrombocyte counts as part of the immune system response against Plasmodium infection.


Assuntos
Antimaláricos , Extratos Vegetais , Plasmodium berghei , Strychnos , Comprimidos , Antimaláricos/toxicidade , Antimaláricos/farmacologia , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Camundongos , Masculino , Strychnos/química , Plasmodium berghei/efeitos dos fármacos , Administração Oral , Estricnina/análogos & derivados , Estricnina/toxicidade , Estricnina/farmacologia , Feminino , Malária/tratamento farmacológico , Testes de Toxicidade Aguda , Dose Letal Mediana
2.
Steroids ; 194: 109222, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36924816

RESUMO

The root bark of Strychnos innocua has long been employed by traditional healers to treat a variety of ill health conditions including fungal infections. The objective of this study was to isolate, characterized and evaluate the antifungal potential (insilico approach) of some steroids from root bark of S. innocua. Conventional method of column chromatography was carried out on the ethyl acetate root bark extract of S. innocua, leading to the isolation of two steroids. On the basis of 1D NMR, 2D NMR, GC-ESI/MS analyses, and literature comparisons, the compounds were characterized as Stigmast-5-en-3ß-ol (1) and Campest-5-en-3ß-ol (2). This is the first time these compounds have been isolated from the plant. The results of the in silico modelling of the compounds 1, 2, and fluconazole (control drug) with the binding sites of SAP2 from Candida albicans (PDB: 1EAG) demonstrated that the binding energies were -8.3, -8.0, and -7.1 kcal/mol, respectively. However, the modelling with binding sites of a deglycating enzyme fructosamine oxidase from Aspergillus fumigatus (PDB: 3DJE) demonstrated that the binding energies were -5.9, -7.2, and -8.0 for Stigmast-5-en-3ß-ol (1) and Campest-5-en-3ß-ol (2), and fluconazole, respectively. In conclusion, the study found that Stigmast-5-en-3-ol and Campest-5-en-3-ol are both present in the root bark of S. innocua. The compounds exhibited promising interaction with the binding sites of the protein target (SAP2 from C. albicans) compare to fluconazole.


Assuntos
Antifúngicos , Esteroides , Strychnos , Antifúngicos/química , Antifúngicos/farmacologia , Simulação por Computador , Fluconazol/química , Fluconazol/farmacologia , Casca de Planta/química , Raízes de Plantas/química , Esteroides/química , Strychnos/química
3.
Phytochemistry ; 203: 113353, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36007664

RESUMO

Seven undescribed monoterpenoid indole alkaloids, two N(4)-chloromethylation artifacts, and 10 known alkaloids were isolated from the stems and twigs of Strychnos cathayensis. The corresponding structures were elucidated via spectroscopic data interpretation and electronic circular dichroism. The absolute configuration of (17S)-12-hydroxy-11-methoxydiaboline, the major anomer of 12-hydroxy-11-methoxydiaboline, was characterized by X-ray diffraction analysis for the first time. At an intraperitoneal dose of 30 mg/kg, 12-hydroxy-11-methoxy-N(4)-chloromethyldiaboline and (-)-macusine A exhibited potential analgesic effects with prolongation rates of 99% and 47% for the latency time of hind-paw licking, respectively, compared to the blank control. 12-Hydroxy-11-methoxydiaboline, 12-hydroxy-11-methoxydiaboline N(4)-oxide, retuline N-oxide, and (-)-vincosamide exhibited antiviral activity against Coxsackie virus B3 (CVB3) with IC50 values of 33.33 µM.


Assuntos
Alcaloides de Triptamina e Secologanina , Strychnos , Analgésicos , Antivirais , Alcaloides Indólicos/química , Estrutura Molecular , Óxidos , Alcaloides de Triptamina e Secologanina/química , Strychnos/química
4.
Toxicon ; 215: 57-68, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35690276

RESUMO

INTRODUCTION: Plants of the Strychnos genus, which include about 200 species, are used for multiple traditional purposes as hunting poison, for example, and have shown interesting pharmacological properties, especially curarizing and tetanizing, but also against malaria. Many monoterpene indole alkaloids have already been isolated and identified. Among them, there is strychnine, a famous alkaloid that can cause death by asphyxiation. OBJECTIVE: Investigate alkaloidic molecular diversity from Strychnos genus using molecular networking technique and study the Strychnos genus from a chemotaxonomic point of view. MATERIAL AND METHODS: Twenty-eight different species and different plant parts were ground into powder using a grinder. The methanolic extracts were carried out using a pressurized solvent extraction and the alkaloid extract was performed manually with a separating funnel. The extracts were analyzed by HPLC-ESI(+)-Q/TOF. The data were processed using MZmine 2 software and the molecular network was generated on the GNPS platform. The study of the generated molecular network allowed the detection of various alkaloids. Among these is the famous strychnine which has been detected in 7 new Strychnos species not yet described as strychnine producers. This identification was investigated using orthogonal approaches, namely TLC, NMR, HPLC-UV and UHPLC-ESI(+)-Q/TOF analyses. The LOD by HPLC-UV of strychnine was also determined. RESULTS: Further analyses allowed to confirm the presence of strychnine in S. densiflora trunk barks but also to show the presence of strychnine with high probability in the trunk barks of S. camptoneura, S. congolana, S. boonei, and S. tchibangensis, and in the leaves of S. usambarensis. About the trunk barks of S. tricalyisoides, the probability of a strychnine content remains low. CONCLUSION: This work exemplified the efficiency of molecular networking in identifying known metabolites (major and minor alkaloids) involved in the chemotaxonomic study of plants from Strychnos genus.


Assuntos
Alcaloides , Strychnos , Alcaloides/química , Alcaloides Indólicos , Folhas de Planta , Estricnina/química , Estricnina/farmacologia , Strychnos/química
5.
J Org Chem ; 87(8): 5199-5212, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35275636

RESUMO

The complex structures and important biological functions of Strychnos alkaloids have attracted a great deal of attention from synthetic chemists. Herein, we describe the concise asymmetric total syntheses of the Strychnos alkaloids, (-)-dehydrotubifoline, (-)-tubifoline, and (-)-tubifolidine, as well as the formal total synthesis of (-)-strychnine. Our strategy features the construction of the common tetracyclic pyrrolo[2,3-d]carbazole structure using regioselective Fischer indolization on unsymmetrical cyclic ketones and late-stage functionalization for divergent synthesis. We developed a stepwise Fischer indolization featuring selective formation of enol triflate to solve the challenging regioselectivity problem, leading to the common tetracyclic ring skeleton in these Strychnos alkaloids. The regioselectivity of Fischer indolization on unsymmetrical cyclic ketones was studied on the basis of different types of ring systems and supported by density functional theory calculations. Overall, our success in the construction of this tetracyclic ring secured the syntheses of Strychnos alkaloids and may provide a general method for the total syntheses of various alkaloids containing this skeleton.


Assuntos
Alcaloides , Strychnos , Alcaloides/química , Cetonas , Estricnina/química , Strychnos/química
6.
J Ethnopharmacol ; 283: 114704, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34601082

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Spiny monkey orange (Strychnos spinosa Lam.) is an African endemic fruit tree that is widely consumed by humans and animals for its nutritional value. In folk medicine, different parts of S. spinosa are widely used for the management of the health and well-being of humans and livestock. AIM: We provide a critical appraisal on the ethnobotanical uses, nutritional and pytochemical as well as the biological activities of S. spinosa. METHODS: Articles were mined from online databases such as Google Scholar, PubMed, Science Direct, SciELO and SpringerLink. We captured research outputs that aligned with the scope of the review. RESULTS: Strychnos spinosa remains a commonly consumed fruit due to its high nutritional (e.g. carbohydrates, crude protein and fats) content and energy. In folk medicine, different parts of S. spinosa are prescribed as remedy for diverse medical conditions especially for treating malaria, diabetes, snakebites, skin-related conditions and sexually transmitted infections in humans as well as sleeping sickness in livestock. Together with essential oils, more than 25 compounds have been profiled using Gas chromatography-mass spectrometry (GC-MS), and approximately 45 compounds have been isolated and structurally elucidated using diverse spectroscopic techniques such as UV-visible, Infrared (IR), Nuclear Magnetic Resonance (NMR) and mass spectroscopy (MS). Strychnos spinosa exerts varying degrees of biological activities against different microorganisms (bacteria and fungi) and parasites (plasmodia, trypanosomes and ticks) responsible for many diseases in humans and livestock. Furthermore, low to moderate enzyme-inhibitory effects of S. spinosa extracts suggest its ability to mitigate pains, inflammations and diabetics as well as snakebite venom. Increasing evidence from the in vivo studies support the use of the plant as a popular remedy for managing diabetics in folk medicine. The low cytotoxic effect of the plant extracts against different cell lines could be an indication of its relative safety. CONCLUSION: Strychnos spinosa exhibits various health-promoting benefits due to its diverse nutritional and phytochemical constituents. Given that the majority of the existing evidence on these aforementioned therapeutic properties and safety are in vitro-based, the clinical significance of these results remain limited.


Assuntos
Medicinas Tradicionais Africanas/métodos , Extratos Vegetais/farmacologia , Strychnos/química , Animais , Etnobotânica , Etnofarmacologia , Frutas , Humanos , Extratos Vegetais/efeitos adversos
7.
Angew Chem Int Ed Engl ; 59(40): 17556-17564, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32476195

RESUMO

We describe enantioselective syntheses of strychnos and chelidonium alkaloids. In the first case, indole acetic acid esters were established as excellent partner nucleophiles for enantioselective cooperative isothiourea/Pd catalyzed α-alkylation. This provides products containing indole-bearing stereocenters in high yield and with excellent levels of enantioinduction in a manner that is notably independent of the N-substituent. This led to concise syntheses of (-)-akuammicine and (-)-strychnine. In the second case, the poor performance of ortho-substituted cinnamyl electrophiles in the enantioselective cooperative isothiourea/Ir catalyzed α-alkylation was overcome by appropriate substituent choice, leading to enantioselective syntheses of (+)-chelidonine, (+)-norchelidonine, and (+)-chelamine.


Assuntos
Alcaloides/química , Chelidonium/química , Strychnos/química , Alcaloides/síntese química , Alquilação , Benzofenantridinas/síntese química , Benzofenantridinas/química , Alcaloides de Berberina/síntese química , Alcaloides de Berberina/química , Catálise , Chelidonium/metabolismo , Humanos , Indóis/síntese química , Indóis/química , Irídio/química , Paládio/química , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo , Estereoisomerismo , Estricnina/síntese química , Estricnina/química , Strychnos/metabolismo , Tioureia/química
8.
Org Biomol Chem ; 18(6): 1046-1056, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31971201

RESUMO

The fascinating structure of Strychnos alkaloids has evoked immense synthetic interest from the chemical community since the landmark synthesis of strychnine by Woodward. After that, the pursuit of the total synthesis of Strychnos alkaloids has never stopped. In this context, the synthesis of strychnine has become a benchmark for the evaluation of new synthetic strategies. Furthermore, the characteristic structure of these alkaloids has also served as an inspiration for the development of novel synthetic methodologies, which provide new synthetic strategies for the synthesis of Strychnos alkaloids. In this article, the recent progress in the total synthesis of Strychnos alkaloids since 2011 is reviewed, including successful total syntheses and synthetic efforts toward Strychnos alkaloids. According to the key feature employed in the synthesis, the content was categorized into novel synthetic methodologies and innovative strategies based on well-documented methodologies.


Assuntos
Alcaloides/síntese química , Strychnos/química , Alcaloides/química , Conformação Molecular
9.
Drug Chem Toxicol ; 43(5): 539-545, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30212238

RESUMO

Strychnos pseudoquina is a plant species whose stem bark is used as bitter tonic beverage. The phytochemical analysis, as well as quantification of phenolic constituents and antioxidant activity of ethanolic extracts from S. pseudoquina stem bark, and leaves were conducted. The extracts were tested for mutagenicity (Ames test) and DNA-damaging activity (Plasmid Cleavage test). Leaves recorded the largest amount of flavonoids. The performed high-performance liquid chromatography (HPLC) showed flavonoids such as isorhamnetin and strychnobiflavone (phytochemical markers of the investigated species) in stem barks, but not in leaves. The proanthocyanidin content and antioxidant activity were significantly higher in stem barks than in leaves. Stem bark and leaf extracts presented mutagenic activity against TA98 and TA100 strains with, and without, metabolic activation (S9). The Plasmid Cleavage test did not indicate DNA-damaging activity. Our results suggest that extracts deriving from S. pseudoquina should be used with extreme caution, mainly the stem bark extract, which is widely used in folk medicine.


Assuntos
Dano ao DNA , Fenóis/análise , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Strychnos/química , Antioxidantes/análise , Antioxidantes/farmacologia , Etanol/química , Flavonoides/análise , Testes de Mutagenicidade , Compostos Fitoquímicos/análise , Folhas de Planta/química , Caules de Planta/química , Proantocianidinas/análise , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
10.
Magn Reson Chem ; 58(6): 532-539, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31663170

RESUMO

The density functional theory calculation of 1 H and 13 C NMR chemical shifts in a series of ten 10 classically known Strychnos alkaloids with a strychnine skeleton was performed at the PBE0/pcSseg-2//pcseg-2 level. It was found that calculated 1 H and 13 C NMR chemical shifts provided a markedly good correlation with experiment characterized by a mean absolute error of 0.08 ppm in the range of 7 ppm for protons and 1.67 ppm in the range of 150 ppm for carbons, so that a mean absolute percentage error was as small as ~1% in both cases.


Assuntos
Alcaloides/química , Teoria da Densidade Funcional , Strychnos/química , Isótopos de Carbono , Espectroscopia de Ressonância Magnética , Conformação Molecular , Prótons
11.
Rapid Commun Mass Spectrom ; 34 Suppl 3: e8683, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31783430

RESUMO

RATIONALE: Monoterpene indole alkaloids (MIAs) are a large group of biologically active compounds produced by hundreds of plant species in numerous plant families, such as Apocynaceae, Loganiaceae and Rubiaceae. Although this diversity is biosynthetically intermediated by strictosidine, there are no works focused on the fragmentation patterns under collision-induced dissociation of strictosidine-derived alkaloids. METHODS: Initially, the alkaloid fingerprint of Strychnos peckii was established using leaf spray with tandem mass spectrometry (LS-MS/MS). Then, high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC/MS/MS) analyses were carried out to focus on the patterns of neutral losses in product ion scan experiments with the leaf aqueous extract. Finally, the product ion spectra from a set of presumable strictosidine-type derivatives were analyzed and organized via molecular networking (MN), and dereplicated by manual interpretation of MS/MS spectra. RESULTS: LS-MS/MS allowed the tentative identification of strictosidine-derived alkaloids in the leaves of S. peckii, showing useful neutral losses for the dereplication of strictosidine analogues by HPLC/MS/MS experiments. The use of MN combined with manual interpretation of the fragmentation patterns highlighted characteristic fragmentation pathways, and allowed the tentative identification of strictosidine, desoxycordifoline, strictosidinic acid, 10-hydroxystrictosidine, 5-carboxystrictosidine, lyaloside, 3,4-dehydrostrictosidine and strictosidine lactam. CONCLUSIONS: The use of MN combined with the analysis of the fragmentation patterns proved to be a useful strategy for the dereplication of strictosidine-derived MIAs from S. peckii, highlighting known and unprecedented structures, as well as useful diagnostic product ions. Therefore, this workflow is an effective approach for the characterization of strictosidine-type alkaloids in future dereplication works.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Alcaloides de Triptamina e Secologanina/análise , Strychnos/química , Espectrometria de Massas em Tandem/métodos , Curare/química , Folhas de Planta/química , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/metabolismo , Processamento de Sinais Assistido por Computador
12.
Chemistry ; 25(38): 8916-8935, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-30994212

RESUMO

Monoterpenoid indole alkaloids are the major class of tryptamine-derived alkaloids found in nature. Together with their structural complexity, this has attracted great interest from synthetic organic chemists. In this Review, the syntheses of Aspidosperma and Strychnos alkaloids through dearomatization of indoles are discussed.


Assuntos
Alcaloides/síntese química , Aspidosperma/química , Técnicas de Química Sintética/métodos , Strychnos/química , Alcaloides/química , Reação de Cicloadição/métodos , Alcaloides de Triptamina e Secologanina/síntese química , Alcaloides de Triptamina e Secologanina/química
13.
Chemistry ; 25(16): 4062-4066, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30620121

RESUMO

Air and visible light have been used in facile direct C-H oxidation of cyclic tertiary amines at ambient conditions, employing organic dyes as photocatalysts and LED. Tolerance of this new environmentally compatible protocol to various side-chain derivatizations of tryptoline and tetrahydroisoquinoline substrates was demonstrated. The developed method provides a straightforward and sustainable route towards δ-lactams, which feature strong antiviral properties (EC50 down to 4.6±1.8 µm) against human cytomegalovirus (HCMV). The clear advantages, which are easily available and inexpensive reagents, organic dyes, visible light, air/O2 and atom efficiency, make this system highly appealing for synthesis of versatile Strychnocarpine alkaloid derivatives with antiviral activity.


Assuntos
Alcaloides/farmacologia , Aminas/química , Antivirais/farmacologia , Citomegalovirus/efeitos dos fármacos , Strychnos/química , Carbolinas/química , Radicais Livres/química , Luz , Estrutura Molecular , Oxirredução , Oxigênio/química , Processos Fotoquímicos , Tetra-Hidroisoquinolinas/química
14.
PLoS One ; 13(8): e0202415, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30118502

RESUMO

Strychnos cocculoides fruit is an important food source for rural populations in Zimbabwe in times of scarcity. Its thick pulp tightly adheres to its seeds, causing pulp extraction constraints and waste during processing, leading to underutilisation. Therefore, pectinase maceration combined with heat treatments was studied to improve juice yield and juice quality. Metabolite profiling according to the heat map, FancyTile chromatic scale approach and phenolic compound content were used to compare the identified compounds. Prior to treatments, 16 known phenolic compounds, predominantly belonging to the phenolic acids, flavonoids and iridoid glucoside classes, were tentatively characterized for the first time in S. cocculoides using High Resolution Mass Spectrometry and LC/MS/MS. Overall, results showed that enzymatic treatments increased pulp yield (by 26%), physicochemical quality (38% increase in juice clarity), content of phenolic compounds (predominantly kaempferol, quercetin, caffeic acid, protocatechuic acid, iridoids) and antioxidant activity.The improved extraction of S. cocculoides pulp increases juice yield as well as juice quality by supplying larger amounts of phenolic compounds that have potential health benefits and act as dietary sources of antioxidants for the prevention of diseases caused by oxidative stress.


Assuntos
Sucos de Frutas e Vegetais , Frutas/química , Temperatura Alta , Proteínas de Plantas/química , Poligalacturonase/química , Polifenóis/análise , Strychnos/química , Polifenóis/química
15.
Planta Med ; 84(12-13): 881-885, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29929205

RESUMO

Strychnogucine B is a bisindole alkaloid previously isolated from Strychnos icaja that possesses promising in vitro antiplasmodial properties. This compound was synthesized in four steps from (-)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its in vivo antimalarial activity was determined intraperitoneally at 30 mg/kg/d in a Plasmodium berghei murine model. In the Peters's 4-d suppressive test, this alkaloid suppressed the parasitaemia by almost 36% on day 5 and 60% on day 7 compared to vehicle-treated mice. In addition to this interesting antimalarial activity, it showed moderate in vitro antitrypanosomal activity but no in vivo activity in an acute Trypanosoma brucei model. It was also inactive in vitro on Leishmania mexicana promastigotes. This highlights its selective antimalarial efficacy and leads to further investigation to assess its potential as new antimalarial lead compound.


Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Plasmodium berghei/efeitos dos fármacos , Estricnina/análogos & derivados , Strychnos/química , Tripanossomicidas/farmacologia , Alcaloides/química , Animais , Antimaláricos/química , Modelos Animais de Doenças , Feminino , Leishmania mexicana/efeitos dos fármacos , Camundongos , Estricnina/química , Estricnina/farmacologia , Tripanossomicidas/química , Trypanosoma brucei brucei/efeitos dos fármacos
16.
PLoS One ; 13(4): e0195786, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29649320

RESUMO

Natural substances are used in folk medicines to treat injuries. Strychnos pseudoquina has scarring, antipyretic, and antimalarial actions. The present study aimed to analyze the effect of S. pseudoquina on cutaneous wound healing in rats. The S. pseudoquina extract was submitted to phytochemical prospection. The levels of flavonoids and total phenolic compounds in the extract were 50.7 mg/g and 2.59 mg/g, respectively. Thirty Wistar rats were individualized in cages with food and water ad libitum (registration no. 730/2014). After anesthesia, three circular wounds (12mm diameter) were made in the animals, which were randomly separated into five treatments: Sal, saline; VO, ointment vehicles (lanolin and Vaseline); SS, positive control (silver sulfadiazine 1%); LE 5, freeze-dried extract 5%; and LE 10, lyophilized extract 10%. The animals were treated with the ointment daily for 21 days. Every seven days, the area and the rate of wound contraction were evaluated. Tissue samples were removed for histopathological analysis of the number of mast cells, elastic and collagen fibers, and biochemical analyses, quantification of malondialdehyde (MDA), carbonylated proteins (PCN), superoxide dismutase (SOD), catalase (CAT), transforming growth factor ß (TGF-ß), Interleukin 10 (IL-10) and tumor necrosis factor (TNF). The number of mast cells, collagen and elastic fibers in the rat wounds were higher in the treatments with the plant. The extract also stimulated the activity of antioxidant enzymes, particularly SOD, presenting high levels, and maintained low levels of PCN. The TGF-ß and IL-10 concentration was higher in the LE5 and LE10 treatment of the extract than in the Sal, OV and SS treatments on day 7. The ointment based on S. pseudoquina closed the wound faster and accelerated wound healing in animals.


Assuntos
Cicatriz/patologia , Extratos Vegetais/farmacologia , Strychnos/química , Cicatrização/efeitos dos fármacos , Animais , Cicatriz/tratamento farmacológico , Colágeno/genética , Colágeno/metabolismo , Citocinas/genética , Citocinas/metabolismo , Expressão Gênica , Imuno-Histoquímica , Masculino , Ratos , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/patologia
17.
Chemistry ; 24(16): 4026-4032, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29168592

RESUMO

Ynamides, as versatile synthetic precursors, have attracted much attention from synthetic chemists and sparked the development of a number of methodologies for the construction of various structures. 1H-Pyrrolo[2,3-d]carbazole is a core scaffold of a series of monoterpene indole alkaloids found in Kopsia, Strychnos, and Aspidosperma, for example. In this study, 1H-pyrrolo[2,3-d]carbazole derivatives were synthesized by a Brønsted acid-catalyzed tandem cyclization starting from tryptamine-based ynamides. This strategy prevented Wagner-Meerwein rearrangement by instantaneous intramolecular nucleophilic trapping of the indoleninium to afford a tetracyclic indoline via an in situ-formed enol species induced by the formation of a more stable conjugate diene moiety. The functional group tolerances were investigated by using a series of readily available substrates. A plausible mechanism has been proposed based on the evidence of the capture of the hemiaminal intermediate. Lastly, a Büchi ketone, which is the pivotal intermediate in the synthesis of the indole alkaloid vindorosine, was synthesized by utilizing our newly developed methodology.


Assuntos
Aspidosperma/química , Carbazóis/síntese química , Alcaloides Indólicos/química , Strychnos/química , Triptaminas/química , Carbazóis/química , Ciclização , Cetonas/química , Estrutura Molecular
18.
Nat Prod Res ; 32(13): 1532-1536, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29022360

RESUMO

Phytochemical investigation of Strychnos nitida has led to the isolation of three new racemic pyridocarbazole alkaloids, (±)-stritidas A-C (1-3) and three known monoterpenoid indole alkaloids (4-6). Compounds 2 and 3 represent the first examples of pyridocarbazole alkaloids featuring an N-2-hydroxyethyl moiety. Their structures were determined by combined spectroscopic data (MS, UV, IR and NMR) and chemical methods.


Assuntos
Alcaloides/química , Carbazóis/química , Strychnos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Alcaloides de Triptamina e Secologanina/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Estereoisomerismo
19.
Biomed Res Int ; 2017: 9538351, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29057272

RESUMO

The effect of topical application of ointment based on Strychnos pseudoquina hydroethanolic extract in the cutaneous wounds healing in diabetic rats was evaluated. Samples of S. pseudoquina were submitted to phytochemical prospection and in vitro antioxidant assay. Thirty Wistar rats were divided into 5 groups: Sal-wounds treated with 0.9% saline solution; VH-wounds treated with 0.6 g of lanolin cream (vehicle); SS-wounds treated with silver sulfadiazine cream (10 mg/g); ES5- and ES10-wounds treated with an ointment of S. pseudoquina extract, 5% and 10%, respectively. Fragments of wounds were removed for histological and biochemical analysis every 7 days during 21 days. ES showed equivalent levels per gram of extract of total phenols and flavonoids equal to 122.04 mg for TAE and 0.60 mg for RE. The chlorogenic acid was one of the major constituents. S. pseudoquina extract presented high antioxidant potential in vitro. ES5 and ES10 showed higher wound healing rate and higher amount of cells, blood vessels, and type III and I collagen. The oxidative stress markers were lower in the ES5 and ES10 groups, while the antioxidants enzymes levels were higher. Ointment based on S. pseudoquina extract promotes a fast and efficient cutaneous repair in diabetic rats.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Cicatriz/tratamento farmacológico , Cicatriz/patologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Humanos , Pomadas/administração & dosagem , Pomadas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia/métodos , Extratos Vegetais/química , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/patologia , Strychnos/química
20.
BMC Complement Altern Med ; 17(1): 13, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056932

RESUMO

BACKGROUND: Malaria is a major public health problem in the world which is responsible for death of millions particularly in sub-Saharan Africa. Today, the control of malaria has become gradually more complex due to the spread of drug-resistant parasites. Medicinal plants are the unquestionable source of effective antimalarials. The present study aimed to evaluate antiplasmodial activity and acute toxicity of the plant Strychnos mitis in Plasmodium berghei infected mice. METHODS: Standard procedures were employed to investigate acute toxicity and 4-day suppressive effect of crude aqueous and hydro-methanolic extracts of the leaves of Strychnos mitis against P. berghei in Swiss albino mice. Water, n-hexane and chloroform fractions, obtained from crude hydro-methanolic extract, were also tested for their suppressive effect against P. berghei. RESULTS: All crude extracts revealed no obvious acute toxicity in mice up to the highest dose administered (2000 mg/kg). All crude and solvent fractions of the leaves of Strychnos mitis inhibited parasitaemia significantly (p < 0.01). At the highest dose of 600 mg/kg, both aqueous and hydro-methanolic extracts demonstrated higher performance with 95.5 and 93.97% parasitaemia suppression, respectively. All doses of crude extracts and fractions of leaves of Strychnos mitis prolonged survival time of infected mice dose dependently. The highest two doses of the crude aqueous and hydro-methanolic extracts, and chloroform and aqueous fractions prevented weight loss in a dose dependent manner. Whereas, all doses of n-hexane fraction prevented loss of body weight but not in a dose dependent manner. The crude aqueous extract at the doses of 400 mg/kg and 600 mg/kg and hydro-methanolic extract at all dose levels significantly (p < 0.01) prevented packed cell volume reduction. Crude aqueous extract at a dose of 600 mg/kg and hydro-methanolic extract at all dose levels significantly prevented temperature reduction. Phytochemical screening of the crude aqueous and hydro-methanolic extracts revealed the presence of alkaloids, anthraquinones, glycosides, terpenoids, saponins, tannins and phenols. CONCLUSION: The results of this study provide support the traditional therapeutic use of Strychnos mitis for treatment of malaria. However, further in-depth study is needed to evaluate the potential of the plant towards the development of new antimalarial agent.


Assuntos
Antimaláricos/administração & dosagem , Malária/parasitologia , Extratos Vegetais/administração & dosagem , Plasmodium berghei/efeitos dos fármacos , Strychnos/química , Animais , Antimaláricos/química , Antimaláricos/isolamento & purificação , Humanos , Malária/tratamento farmacológico , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Plasmodium berghei/fisiologia
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