RESUMO
Pesticides are used to control and combat insects and pests in the agricultural sector, households, and public health programs. The frequent and disorderly use of these pesticides may lead to variety of undesired effects. Therefore, natural products have many advantages over to synthetic compounds to be used as insecticides. The goal of this study was to find natural products with insecticidal potential against Musca domestica and Mythimna separata. To achieve this goal, we developed predictive QSAR models using MuDRA, PLS, and RF approaches and performed virtual screening of 117 natural products. As a result of QSAR modeling, we formulated the recommendations regarding physico-chemical characteristics for promising compounds active against Musca domestica and Mythimna separata. Homology models were successfully built for both species and molecular docking of QSAR hits vs known insecticides allowed us to prioritize twenty-two compounds against Musca domestica and six against Mythimna separata. Our results suggest that pimarane diterpenes, abietanes diterpenes, dimeric diterpenes and scopadulane diterpenes obtained from aerial parts of species of the genus Calceolaria (Calceolariaceae: Scrophulariaceae) can be considered as potential insecticidal.
Assuntos
Dípteros/efeitos dos fármacos , Diterpenos/química , Diterpenos/farmacologia , Inseticidas/farmacologia , Animais , Desenho de Fármacos , Moscas Domésticas/efeitos dos fármacos , Modelos Biológicos , Estrutura Molecular , Relação Quantitativa Estrutura-Atividade , Scrophulariaceae/química , Sensibilidade e EspecificidadeRESUMO
Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution method for determining the minimum inhibitory concentration (MIC) against six bacterial strains. Tests have shown that these derivatives have potential against all bacterial strains. The cytotoxic activity was also evaluated against three strains of cancer cells, but none of the derivatives showed activity.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Hidrazonas/farmacologia , Naftoquinonas/farmacologia , Oximas/farmacologia , Scrophulariaceae/química , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Testes de Sensibilidade Microbiana , Naftoquinonas/síntese química , Naftoquinonas/química , Neoplasias/tratamento farmacológico , Oximas/síntese química , Oximas/químicaRESUMO
Capraria biflora L. is a shrub from the Scrophulariaceae family which produces in its roots a compound named biflorin, an o-naphthoquinone that shows activity against Gram-positive bacteria and fungi and also presents antitumor and antimetastatic activities. However, biflorin is hydrophobic and photosensitive. These properties make its application difficult. In this work we prepared biflorin micellar nanostructures looking for a more effective vehiculation and better preservation of the biological activity. Biflorin was obtained, purified and characterized by UV-Vis, infrared (IR) and 1H- and 13C-NMR. Micellar nanostructures of biflorin were then assembled with Tween 80®, Tween 20® and saline (0.9%) and characterized by UV-Vis spectroscopy and dynamic light scattering (DLS). The results showed that the micellar nanostructures were stable and presented an average size of 8.3 nm. Biflorin micellar nanostructures' photodegradation was evaluated in comparison with biflorin in ethanol. Results showed that the biflorin in micellar nanostructures was better protected from light than biflorin dissolved in ethanol, and also indicated that biflorin in micelles were efficient against Gram-positive bacteria and yeast species. In conclusion, the results showed that the micellar nanostructures could ensure the maintenance of the biological activity of biflorin, conferring photoprotection. Moreover, biflorin vehiculation in aqueous media was improved, favoring its applicability in biological systems.
Assuntos
Anti-Infecciosos/farmacologia , Candida/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Naftoquinonas/farmacologia , Anti-Infecciosos/química , Micelas , Testes de Sensibilidade Microbiana , Nanoestruturas/química , Naftoquinonas/química , Raízes de Plantas/química , Scrophulariaceae/químicaRESUMO
Biflorin is an o-naphthoquinone isolated from the roots of the plant Capraria biflora L. (Scrophulariaceae). In this study, the cytotoxic effects of biflorin were verified, and late apoptosis was detected in various cancer cell lines by in situ analysis. The cytotoxicity was further evaluated exclusively for 48 h of treatment in different tumor and non-tumor cell lines (Hep-2, HeLa, HT-29, A-375, and A-549, and HEK-293, respectively). The results indicated that biflorin induced selective cytotoxicity in tumor cells. HeLa cells were more susceptible to biflorin, followed by HT-29, A-549, A-375, and Hep-2 at all concentrations (range 5-50 µg/mL), and the highest half-maximal inhibitory concentration IC50 (56.01 ± 1.17 µg/mL) was observed in HEK-293 cells. Late apoptotic/necrotic events, observed by in situ immunostaining with Annexin V, varied with each cell line; an increase in late apoptotic events was observed corresponding to the increase in biflorin dosage. Hep-2 cells showed a greater percentage of late apoptotic events among the tumor cell lines when treated with higher concentrations of biflorin (69.63 ± 2.28%). The non-tumor HEK-293 line showed greater resistance to late apoptotic events, as well as a lower level of cytotoxicity (77.69 ± 6.68%) than the tested tumor lines. The data presented indicate that biflorin showed an important, possibly selective, cytotoxicity against tumor cell lines, thereby revealing a promising novel substance with potential anticancer activity for tumor therapy.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Naftoquinonas/administração & dosagem , Neoplasias/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Células HEK293 , Humanos , Naftoquinonas/química , Neoplasias/patologia , Scrophulariaceae/químicaRESUMO
A new iridoid glucoside has been isolated from the Chilean native Alonsoa meridionalis (L.f.) Kuntze. Its structure has been assigned as 6'-O-ß-d-glucopyranosyl-8-O-acetylharpagide (1) by using spectroscopic methods. Harpagoside (2), laterioside (3) and verbascoside (4) were also identified.
Assuntos
Glicosídeos Iridoides/isolamento & purificação , Scrophulariaceae/química , Chile , Glicosídeos , Glicosídeos Iridoides/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , PiranosRESUMO
Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Naftoquinonas/farmacologia , Scrophulariaceae/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Naftoquinonas/química , Naftoquinonas/isolamento & purificaçãoRESUMO
As a defense mechanism of the aerial parts of Calceolaria talcana (Calceolariaceae; formerly Scrophulariaceae) against herbivore offenses and insect pest attack, diterpenoids, triterpenoids, phenylethanoids, flavonoids, and iridoids are rapidly accumulated along the aerial parts, resulting in a unique natural biopesticide complex from this plant. In addition to verbascoside a series of known compounds were screened for their inhibitory activity against mushroom tyrosinase and protease enzymes. Ethyl acetate and n-hexane extracts, together with cyclopropyl-7,15-ent-pimaradiene (1), abietatriene (2), ursolic acid (3), α-lupeol (4), ß-sitosterol (5), 2-hydroxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (6), α-dunnione (7), verbascoside (8), martynoside (9), and some known model compounds proved to be inhibitors of oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase (EC 1.14.18.1) with an IC50 between 10.0 and 200 ppm or µM, respectively, suggesting that phenolic moieties in the molecules assayed are important for the activity.
Assuntos
Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/química , Scrophulariaceae/química , Acetatos/química , Agaricales/enzimologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Agentes de Controle Biológico , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Hexanos/química , Concentração Inibidora 50 , Insetos , Iridoides/isolamento & purificação , Iridoides/farmacologia , Monofenol Mono-Oxigenase/metabolismo , Praguicidas/química , Praguicidas/isolamento & purificação , Praguicidas/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Inibidores de Proteases/isolamento & purificação , Inibidores de Proteases/farmacologiaRESUMO
(+)-2-Deoxyoryzalexin S (1), the nominal enantiomer of a diterpenoid isolated in Chile from Calceolaria species, was regio- and diastereoselectively synthesized from (+)-podocarpic acid. (+)-2-Deoxyoryzalexin S (1) was characterized also as its acetyl derivative, (+)-2, whose structure was confirmed by X-ray crystallographic analysis. Surprisingly, comparison of the data recorded for (+)-1 and (+)-2 and those reported in the literature for the Calceolaria isolated diterpenoid 1 and its derivative (-)-2 showed some differences, suggesting that the latter do not possess the proposed structures.
Assuntos
Abietanos/química , Scrophulariaceae/química , Chile , Cristalografia por Raios X , Diterpenos , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A series of analogues, derived from the antiviral and cytotoxic diterpene stemodin, were prepared and evaluated for their lipid peroxidation (LPO), cyclooxygenase enzyme-1 (COX-1) and -2 (COX-2), and tumour cell proliferation inhibitory activities. Oxidation of stemodin produced stemodinone, which was then converted to stemod-12-en-2-one. Reaction of the latter under Petrow conditions (bromine; silver acetate/pyridine) yielded mainly dibrominated abeo-stachanes. Solvolysis of the dibromo compounds gave products of hydrolysis, some with rearranged skeleta. In the lipid peroxidation inhibitory assay three of the compounds exhibited prominent activity. Interestingly, all the analogues showed higher COX-1 enzyme inhibition than COX-2. Although a few of the diterpenes limited the growth of some human tumour cell lines, most compounds induced proliferation of such cells.
Assuntos
Antineoplásicos Fitogênicos/química , Inibidores de Ciclo-Oxigenase/química , Diterpenos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Scrophulariaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/isolamento & purificação , Inibidores de Ciclo-Oxigenase/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , OxirreduçãoRESUMO
Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi-drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25-12.50 µg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, from 1H NMR full spin analysis, and by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers.
Assuntos
Antituberculosos/isolamento & purificação , Antituberculosos/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Scrophulariaceae/química , Antituberculosos/química , Dicroísmo Circular , Diterpenos/química , México , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Raízes de Plantas/químicaRESUMO
We evaluated the effects of saline stress on soluble proteins, lipid peroxidation (TBAR), chlorophyll a, chlorophyll b, beta-carotene, violaxanthin, and proline in Paulownia imperialis and Paulownia fortunei plants grown in vitro. When the propagated plants reached a determined size, they were transferred aseptically to WPM culture medium containing different sodium chloride concentrations (0, 20, 40, 60, 80, and 160 mM) and were sampled at 15 and 30 days. Proline content was determined at 30 days after transfer only. Protein concentration significantly decreased with the highest salt levels in P. imperialis compared to controls in which no sodium chloride was added. In both P. imperialis and P. fortunei, lipid peroxidation significantly increased at 15 days but decreased at 30 days. Chlorophyll a, chlorophyll b, beta-carotene, and violaxanthin significantly decreased with exposure to higher sodium chloride concentrations at 15 and 30 days in both species. Proline content in P. imperialis significantly increased in plants grown in 20 and 40 mM of sodium chloride and decreased in higher sodium chloride concentrations. In P. fortunei, this measure significantly decreased proline content at all salt concentrations in plants exposed to all levels of sodium chloride compared to controls. Our results show that P. imperialis is more tolerant to salt stress at the salinity conditions tested.
Assuntos
Cloreto de Sódio/farmacologia , Pigmentos Biológicos/análise , Prolina/análise , Proteínas/análise , Scrophulariaceae/metabolismo , Scrophulariaceae/química , Peroxidação de Lipídeos , Pigmentos Biológicos , Prolina , Proteínas , Salinidade , Tolerância ao Sal , Técnicas de Cultura de TecidosRESUMO
Two new labdane diterpenes, 6alpha-malonyloxy-ethyl ester manoyl oxide and bis-6alpha-dioxymanoylmalonate, together with the known 6alpha-hydroxymanoyl oxide, 6alpha-malonyloxymaloyl oxide and betulinic acid were isolated from leaves of Stemodia trifoliata. Their structures were elucidated by spectroscopic studies (IR and HR-ESI-MS), including an extensive NMR (COSY, HSQC, HMBC and NOESY) analysis.
Assuntos
Diterpenos/química , Espectroscopia de Ressonância Magnética/métodos , Extratos Vegetais/química , Scrophulariaceae/química , AcilaçãoRESUMO
As part of a continuing interest in exploring the chemistry of Brazilian medicinal plants, three new labdane diterpenoids, 6alpha-acetoxymanoyl oxide (1), 6alpha-malonyloxymanoyl oxide (2), and 6alpha-malonyloxy-n-butyl ester manoyl oxide (3), together with the known betulinic acid, lupeol, sitosterol, and stigmasterol, were isolated from the aerial parts of Stemodia foliosa. The structures of 1-3 were established on the basis of interpretation of spectroscopic data, including HRESIMS, and 1D and 2D NMR techniques. All compounds were tested against a bacteria panel consisting of Staphylococcus aureus, Bacillus cereus, B. subtilis, B. anthracis, Micrococcus luteus, Mycobacterium smegmatis, and M. phlei. Compound 2 showed moderate activity against these strains, with MIC values in the range 7-20 microg/mL.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Diterpenos/isolamento & purificação , Plantas Medicinais/química , Scrophulariaceae/química , Antibacterianos/química , Bacillus anthracis/efeitos dos fármacos , Bacillus cereus/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Brasil , Diterpenos/química , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Estrutura Molecular , Mycobacterium phlei/efeitos dos fármacos , Mycobacterium smegmatis/efeitos dos fármacos , Triterpenos Pentacíclicos , Sitosteroides/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Estigmasterol/isolamento & purificação , Triterpenos/isolamento & purificação , Ácido BetulínicoRESUMO
A selective route for the degradation of the unsaturated side chain of ent-labdanes has been devised, giving two useful synthons: 2beta-acetoxy-14,15,17-trinor-ent-labdane-8,13- dione (5) and 2beta-acetoxy-14,15-dinor-ent-labd-8(17)-en-13-one (7), the use of which for the preparation of terpenylquinone derivatives shall be reported elsewhere.
Assuntos
Diterpenos/química , Diterpenos/metabolismo , Scrophulariaceae/química , Ressonância Magnética Nuclear Biomolecular , OxirreduçãoRESUMO
Pharmacological studies with an aqueous extract obtained from leaves of Capraria biflora showed potent cytotoxic, analgesic, antimicrobial and anti-inflammatory activities. It has been demonstrated that biflorin possesses an in vitro cytotoxic activity against tumor cells. The in vivo antitumor activity of biflorin was evaluated on two mouse models, sarcoma 180 and Ehrlich carcinoma. Biflorin was active against both tumors with a very similar profile. In addition, biflorin was also able to increase the response elicited by 5-FU in mice inoculated with both tumors. The results showed a decrease in Ki67 staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate. Histopathological analysis from kidneys and liver showed that biflorin possessed weak and reversible toxic effects. It was also demonstrated that biflorin acts as an immunoadjuvant agent, rising the production of ovalbumin-specific antibodies and inducing a discreet increase of the white pulp and nest of megakaryocytic in spleen of treated mice, which can be related to its antitumor properties.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Naftoquinonas/farmacologia , Scrophulariaceae/química , Adjuvantes Imunológicos/farmacologia , Animais , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/isolamento & purificação , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Feminino , Fluoruracila/uso terapêutico , Imuno-Histoquímica , Indicadores e Reagentes , Antígeno Ki-67/metabolismo , Camundongos , Transplante de Neoplasias , Ovalbumina/imunologia , Sarcoma 180/tratamento farmacológico , Sarcoma 180/patologiaRESUMO
The present review focus in quinones found in species of Brazilian northeastern Capraria biflora, Lippia sidoides, Lippia microphylla and Tabebuia serratifolia. The review cover ethnopharmacological aspects including photography of species, chemical structure feature, NMR datea and biological properties. Chemical transformations of lapachol to form enamine derivatives and biological activities are discussed.
Assuntos
Lippia/química , Quinonas/química , Quinonas/farmacologia , Scrophulariaceae/química , Tabebuia/química , Brasil , Espectroscopia de Ressonância MagnéticaRESUMO
Chemical examination of the petrol ether (60-80) extract of the aerial parts of Calceolaria alba R. et Pav., collected in Santa Juana, VIII Region, Chile, resulted in the isolation of 3 new diterpenoids. Their structures have been elucidated by a study of their physical and spectral data; in particular using 2 NMR spectroscopy (DEPT, 1H-1H, COSY, NOESY, HMQC and HMBC).
Assuntos
Diterpenos/química , Scrophulariaceae/química , Diterpenos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
Stemodane and stemarane diterpenes isolated from the plant Stemodia maritima and their dimethylcarbamate derivatives were fed to growing cultures of the fungi Cunninghamella echinulata var. elegans ATCC 8688a and Phanerochaete chrysosporium ATCC 24725. C. echinulata transformed stemodin (1) to its 7alpha-hydroxy- (2), 7beta-hydroxy- (3) and 3beta-hydroxy- (4) analogues. 2alpha-(N,N-Dimethylcarbamoxy)-13-hydroxystemodane (6) gave 2alpha-(N,N-dimethylcarbamoxy)-6alpha,13-dihydroxystemodane (7) and 2alpha-(N,N-dimethylcarbamoxy)-7alpha,13-dihydroxystemodane (8). Stemodinone (9) yielded 14-hydroxy-(10) and 7beta-hydroxy- (11) congeners along with 1, 2 and 3. Stemarin (13) was converted to the hitherto unreported 6alpha,13-dihydroxystemaran-19-oic acid (18). 19-(N,N-Dimethylcarbamoxy)-13-hydroxystemarane (14) yielded 13-hydroxystemaran-19-oic acid (17) along with the two metabolites: 19-(N,N-dimethylcarbamoxy)-2beta,13-dihydroxystemarane (15) and 19-(N,N-dimethylcarbamoxy)-2beta,8,13-trihydroxystemarane (16). P. chrysosporium converted 1 into 3, 4 and 2alpha,11beta,13-trihydroxystemodane (5). The dimethylcarbamate (6) was not transformed by this microorganism. Stemodinone (9) was hydroxylated at C-19 to give 12. Both stemarin (13) and its dimethylcarbamate (14) were recovered unchanged after incubation with Phanerochaete.
Assuntos
Cunninghamella/metabolismo , Diterpenos/metabolismo , Phanerochaete/metabolismo , Scrophulariaceae/química , Biotransformação , Diterpenos/química , Estrutura Molecular , Plantas Medicinais/químicaRESUMO
Secondary metabolites, DIBOA, HBOA, 7-OH-HBOA, BOA and gallic acid, were isolated and quantified from Calceolaria thyrsiflora Graham, a native medicinal plant of Chile belonging to the Scrophulariaceae family. The highest DIBOA contents were determined in leaves (145 mmol kg(-1) dry wt) and flowers (161 mmol kg(-1) dry wt). Antibacterial activities of DIBOA, HBOA, BOA, gallic acid and infusions of flowers and leaves were determined. The phytomedicinal properties attributed to C. thyrsiflora Graham could be understood on the basis of its antibacterial activity.