RESUMO
Kaurane diterpenes are considered important compounds in the development of new highly effective anticancer chemotherapeutic agents. Genotoxic effects of anticancer drugs in non-tumour cells are of special significance due to the possibility that they induce secondary tumours in cancer patients. In this context, we evaluated the genotoxic and mutagenic potential of the natural diterpenoid kaurenoic acid (KA), i.e. (-)-kaur-16-en-19-oic acid, isolated from Xylopia sericeae St. Hill, using several standard in vitro and in vivo protocols (comet, chromosomal aberration, micronucleus and Saccharomyces cerevisiae assays). Also, an analysis of structure-activity relationships was performed with two natural diterpenoid compounds, 14-hydroxy-kaurane (1) and xylopic acid (2), isolated from X. sericeae, and three semi-synthetic derivatives of KA (3-5). In addition, considering the importance of the exocyclic double bond (C16) moiety as an active pharmacophore of KA cytotoxicity, we also evaluated the hydrogenated derivative of KA, (-)-kauran-19-oic acid (KAH), to determine the role of the exocyclic bond (C16) in the genotoxic activity of KA. In summary, the present study shows that KA is genotoxic and mutagenic in human peripheral blood leukocytes (PBLs), yeast (S. cerevisiae) and mice (bone marrow, liver and kidney) probably due to the generation of DNA double-strand breaks (DSB) and/or inhibition of topoisomerase I. Unlike KA, compounds 1-5 and KAH are completely devoid of genotoxic and mutagenic effects under the experimental conditions used in this study, suggesting that the exocyclic double bond (C16) moiety may be the active pharmacophore of the genetic toxicity of KA.
Assuntos
Diterpenos/química , Diterpenos/toxicidade , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Testes de Mutagenicidade , Relação Estrutura-AtividadeRESUMO
The in vivo antifungal activity of the naphthoquinone beta-lapachone against disseminated infection by Cryptococcus neoformans was investigated. Swiss mice were immunosuppressed daily with dexamethasone (0.5 mg per mouse) intraperitoneally for 3 days, the procedure was repeated 4 days later, and the animals were then challenged intravenously with C. neoformans (10(6) CFU/mL) 1 week later. Seven days after infection, the mice were divided into groups and treated daily with beta-lapachone (10 mg/kg, iv) for 7 (N = 6) and 14 days (N = 10). Amphotericin B (0.5 mg/kg) was used as comparator drug and an additional group received PBS. Treatment with beta-lapachone cleared the yeast from the spleen and liver, and the fungal burden decreased approximately 10(4) times in the lungs and brain 14 days after infection when compared to the PBS group (P < 0.05). This result was similar to that of the amphotericin B-treated group. Protection was suggestively due to in vivo antifungal activity of this drug and apparently not influenced by activation of the immune response, due to similar leukocyte cell counts among all groups. This study highlights the prospective use of beta-lapachone for treatment of disseminated cryptococcosis.
Assuntos
Animais , Masculino , Camundongos , Antifúngicos/uso terapêutico , Cryptococcus neoformans , Criptococose/tratamento farmacológico , Hospedeiro Imunocomprometido , Naftoquinonas/uso terapêutico , Dexametasona , Imunossupressores , Contagem de LeucócitosRESUMO
The in vivo antifungal activity of the naphthoquinone beta-lapachone against disseminated infection by Cryptococcus neoformans was investigated. Swiss mice were immunosuppressed daily with dexamethasone (0.5 mg per mouse) intraperitoneally for 3 days, the procedure was repeated 4 days later, and the animals were then challenged intravenously with C. neoformans (10(6) CFU/mL) 1 week later. Seven days after infection, the mice were divided into groups and treated daily with beta-lapachone (10 mg/kg, iv) for 7 (N = 6) and 14 days (N = 10). Amphotericin B (0.5 mg/kg) was used as comparator drug and an additional group received PBS. Treatment with beta-lapachone cleared the yeast from the spleen and liver, and the fungal burden decreased approximately 10(4) times in the lungs and brain 14 days after infection when compared to the PBS group (P < 0.05). This result was similar to that of the amphotericin B-treated group. Protection was suggestively due to in vivo antifungal activity of this drug and apparently not influenced by activation of the immune response, due to similar leukocyte cell counts among all groups. This study highlights the prospective use of beta-lapachone for treatment of disseminated cryptococcosis.
Assuntos
Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Cryptococcus neoformans , Hospedeiro Imunocomprometido , Naftoquinonas/uso terapêutico , Animais , Dexametasona , Imunossupressores , Contagem de Leucócitos , Masculino , CamundongosRESUMO
The antibacterial potential of leaf's essential oil (EO) from Brazilian pepper tree (Schinus terebinthifolius Raddi) against staphylococcal isolates from dogs with otitis externa was evaluated. The minimum inhibitory concentration of EO ranged from 78.1 to 1,250 fg/mL. The oil was analyzed by GC and GC/MS and cytotoxicity tests were carried out with laboratory animals.
Assuntos
Animais , Cães , Animais de Laboratório , Antibacterianos , Anacardiaceae/citologia , Anacardiaceae/toxicidade , Otite Externa , Óleos Voláteis/análise , Óleos Voláteis/toxicidade , Staphylococcus aureus/isolamento & purificação , Métodos , Métodos , Medicina VeterináriaRESUMO
The antibacterial potential of leaf's essential oil (EO) from Brazilian pepper tree (Schinus terebinthifolius Raddi) against staphylococcal isolates from dogs with otitis externa was evaluated. The minimum inhibitory concentration of EO ranged from 78.1 to 1,250 µg/mL. The oil was analyzed by GC and GC/MS and cytotoxicity tests were carried out with laboratory animals.
RESUMO
The essential oils from accessions of Lippia sidoides Cham. (Verbenaceae) were characterized by GC and GC/MS and investigated for their acaricidal activity against the two-spotted spider mite (Tetranychus urticae Koch). Twenty-nine compounds were identified with potential acaricidal activity. Glass receptacles were used as test chambers. For each dose and exposure time combination, three replicates were used. Each replicate consisted of 30 adult females of T. urticae, 10 mites in each leaf disk of Canavalia ensiformis placed in a Petri dish. Increasing amounts of oil or terpene were applied on a blotting paper strip, fixed on the inner surface of the glass recipient cover, corresponding to 2, 4, 6, 8, and 10 microL/L of air, respectively. Exposure periods were 24, 48, and 72 h. Data obtained in these experiments were submitted to probit analysis. The essential oil of L. sidoides, thymol and carvacrol exhibited potent acaricidal activity against T. urticae.
Assuntos
Acaricidas/farmacologia , Lippia/química , Óleos Voláteis/farmacologia , Acaricidas/química , Animais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis/química , TetranychidaeRESUMO
The antibacterial potential of leaf's essential oil (EO) from Brazilian pepper tree (Schinus terebinthifolius Raddi) against staphylococcal isolates from dogs with otitis externa was evaluated. The minimum inhibitory concentration of EO ranged from 78.1 to 1,250 fg/mL. The oil was analyzed by GC and GC/MS and cytotoxicity tests were carried out with laboratory animals.
RESUMO
The essential oils of leaves, stems and inflorescences of Piper marginatum, harvested in the Atlantic forest in the State of Pernambuco, Brazil, were obtained by hydrodistillation. GC and GC-MS analyses revealed the presence of 40 components accounting, respectively, for 99.6%, 99.7% and 99.1% of the leaf, stem and inflorescence oil, the most abundant being (Z)- or (E)-asarone and patchouli alcohol. The essential oil of the inflorescences exhibited potent activity against the 4th instar of Aedes aegypti with LC(10) and LC(50) values of 13.8 and 20.0 ppm, respectively. Furthermore, the inflorescence oil did not interfere in the oviposition of A. aegypti females when assayed at 50 ppm. These properties suggest that P. marginatum oil is a potential source of valuable larvicidal compounds for direct use or in conjunction with baits in traps constructed to capture eggs and larvae.
Assuntos
Aedes/efeitos dos fármacos , Inseticidas/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Oviposição/efeitos dos fármacos , Piperaceae/química , Animais , Feminino , Flores/química , Larva/efeitos dos fármacos , Óleos Voláteis/análise , Folhas de Planta/química , Caules de Planta/química , VolatilizaçãoRESUMO
Over the last five years, collection and periodic observation in the Tapacurá Ecological Station, São Lourenço da Mata, Pernambuco, Brazil, have been carried out to produce a systematic ecological inventory of grasshopper distribution within the station based on the classifying criteria for Acridoidea, providing new data on families, subfamilies, tribes, genera and species related to the various types of vegetation and environments the station affords.
Assuntos
Conservação dos Recursos Naturais , Gafanhotos/classificação , Animais , Brasil , Dinâmica PopulacionalRESUMO
Over the last five years, collection and periodic observation in the Tapacurá Ecological Station, São Lourenço da Mata, Pernambuco, Brazil, have been carried out to produce a systematic ecological inventory of grasshopper distribution within the station based on the classifying criteria for Acridoidea, providing new data on families, subfamilies, tribes, genera and species related to the various types of vegetation and environments the station affords.
Através de procedimento de coletas e observações periódicas, ao longo de cinco anos, na Estação Ecológica do Tapacurá, São Lourenço da Mata, PE, procedeu-se a um inventário sistemático-ecológico da distribuição dos gafanhotos da estação, adotando-se critérios classificatórios de Acridoidea com novos assinalamentos de famílias, subfamílias, tribos, gêneros e espécies, relacionados aos diversos tipos de vegetação e ambientes da estação.
Assuntos
Animais , Conservação dos Recursos Naturais , Gafanhotos/classificação , Brasil , Dinâmica PopulacionalRESUMO
The cytotoxic activity of amino (3a-e), aza-1-antraquinone (4a-e) lapachol derivatives against Ehrlich carcinoma and human K562 leukemia cells was investigated. Cell viability was determined using MTT assay, after 48 (Ehrlich) or 96 h (K562) of culture, and vincristine (for K562 leukemia) and quercetin (for Ehrlich carcinoma) were used as positive controls. The results showed dose-dependent growth-inhibiting activities and that the amino derivatives were active against the assayed cells, whereas the 4a-e derivatives were not. The allylamine derivative 3a was the most active against Ehrlich carcinoma, with IC50 = 16.94 ± 1.25 muM, and against K562 leukemia, with IC50 = 14.11 ± 1.39 muM. The analogous lawsone derivative, 5a, was also active against Ehrlich carcinoma (IC50 = 23.89 ± 2.3 muM), although the 5d and 5e derivatives showed lower activity. The interaction between 3a-d and calf thymus DNA was investigated by fluorimetric titration and the results showed a hyperchromic effect indicating binding to DNA as presented of ethidium bromide, used as positive control. The inhibitory action on DNA-topoisomerase II-a was also evaluated by a relaxation assay of supercoiled DNA plasmid, and the etoposide (200 muM) was used as positive control. Significant inhibitory activities were observed for 3a-d at 200 muM and a partial inhibitory action was observed for lapachol and methoxylapachol.
Assuntos
Animais , Humanos , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Carcinoma de Ehrlich/enzimologia , DNA Topoisomerases Tipo II/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Naftoquinonas/farmacologia , Antineoplásicos Fitogênicos/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/química , /efeitos dos fármacos , Naftoquinonas/química , Quercetina/farmacologia , Vincristina/farmacologiaRESUMO
The cytotoxic activity of amino (3a-e), aza-1-antraquinone (4a-e) lapachol derivatives against Ehrlich carcinoma and human K562 leukemia cells was investigated. Cell viability was determined using MTT assay, after 48 (Ehrlich) or 96 h (K562) of culture, and vincristine (for K562 leukemia) and quercetin (for Ehrlich carcinoma) were used as positive controls. The results showed dose-dependent growth-inhibiting activities and that the amino derivatives were active against the assayed cells, whereas the 4a-e derivatives were not. The allylamine derivative 3a was the most active against Ehrlich carcinoma, with IC50 = 16.94 +/- 1.25 microM, and against K562 leukemia, with IC50 = 14.11 +/- 1.39 microM. The analogous lawsone derivative, 5a, was also active against Ehrlich carcinoma (IC50 = 23.89 +/- 2.3 microM), although the 5d and 5e derivatives showed lower activity. The interaction between 3a-d and calf thymus DNA was investigated by fluorimetric titration and the results showed a hyperchromic effect indicating binding to DNA as presented of ethidium bromide, used as positive control. The inhibitory action on DNA-topoisomerase II-a was also evaluated by a relaxation assay of supercoiled DNA plasmid, and the etoposide (200 microM) was used as positive control. Significant inhibitory activities were observed for 3a-d at 200 microM and a partial inhibitory action was observed for lapachol and methoxylapachol.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma de Ehrlich/enzimologia , Inibidores Enzimáticos/farmacologia , Naftoquinonas/farmacologia , Inibidores da Topoisomerase II , Animais , Antineoplásicos Fitogênicos/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/química , Humanos , Concentração Inibidora 50 , Células K562/efeitos dos fármacos , Camundongos , Naftoquinonas/química , Quercetina/farmacologia , Vincristina/farmacologiaRESUMO
The molluscicidal profile and brine-shrimp bio-activity of the ethanolic extracts of plants from the Bignoniaceae family were determined. The six extracts investigated were of the stems of Melloa quadrivalvis and Tabebuia aurea, and whole plants of Adenocalymma comosum, Arrabidaea parviflora, Cuspidaria argentea and Clytostoma binatum. When tested in the laboratory, with Biomphalaria glabrata as the test snail, all six extracts gave median lethal concentrations (9-54 microg/ml) that fell well below the upper threshold, of 100 mug/ml, set for a potential molluscicide by the World Health Organization.
Assuntos
Bignoniaceae , Biomphalaria/efeitos dos fármacos , Vetores de Doenças , Moluscocidas/farmacologia , Esquistossomose/prevenção & controle , Animais , Moluscocidas/toxicidade , Extratos Vegetais/farmacologia , Esquistossomose/transmissãoRESUMO
Plants in the genus Solanum (Solanaceae) produce a great variety of steroidal saponins and glycoalkaloids that confer natural resistance against several pests. Methanolic extracts of 13 Solanum species have now been tested for molluscicidal activity against Biomphalaria glabrata. The extracts investigated were prepared from the fruit of S. asperum, S. capsicoides, S. palinacantum, S. paludosum, S. paniculatum, S. paraibanum and S. sisymbriifolium, the aerial parts of S. asperum, S. capsicoides, S. crinitum, S. diamantinense, S. megalonyx, S. palinacantum, S. paniculatum, S. sisymbriifolium and S. torvum, and the roots of S. asperum, S. asterophorum, S. palinacantum, S. paludosum, S. paniculatum and S. stipulaceum. Encouragingly, the extracts from S. asperum, S. diamantinese, S. paludosum, S. sisymbriifolium and S. stipulaceum showed significant molluscicidal activity, the median lethal concentrations recorded (20-50 microg/ml) falling well below the threshold, of 100 microg/ml, set for a potential molluscicide by the World Health Organization.
Assuntos
Biomphalaria , Vetores de Doenças , Moluscocidas , Esquistossomose/prevenção & controle , Solanum , Animais , Bioensaio/métodos , Biomphalaria/parasitologia , Extratos Vegetais , Esquistossomose/transmissãoRESUMO
O óleo essencial obtido por hidrodestilação das folhas de Eugenia punicifolia, coletados a partir de duas regiões de Matas Serranas do Estado de Pernambuco (Serra Negra e Brejo da Madre de Deus), foi analisado por CG/EM. O monoterpeno oxigenado, linalol (SN: 44,0 por cento, BMD: 61,2 por cento), foi o componente principal do óleo de ambas amostras. Cerca de 66,2 por cento da constituição dos voláteis da amostra proveniente de SN e 74,2 por cento de BMD referem-se aos monoterpenos oxigenados, enquanto 33,6 por cento da amostra de SN e 20,5 por cento de BMD são sesquiterpenos oxigenados, sendo o b-cariofileno o mais abundante (SN: 22,7 por cento, BMD: 16,2 por cento). Com exceção do a-cadinol, presente apenas no óleo proveniente do Brejo da Madre de Deus, a constituição química de ambas as amostras foi à mesma, variando apenas o percentual relativo de seus constituintes.
The essential oils obtained from the leaves of Eugenia punicifolia by hydrodistillation, which were collected from two different locations of Pernambuco (Serra Negra and Brejo da Madre de Deus), have been investigated by GC/MS. Linalol was found to be the main component of this oil from SN (44,0 percent) and BMD (61,2 percent). About 66,2 percent of the oil constituents from SN and 74,2 percent from BMD are oxygenated monoterpenes, with predominance of beta-cariofileno (SN: 22,7 and BMD: 16,2 percent). With exception of a-cadinol, present only in the oils from plants colleted in Brejo da Madre de Deus, the chemical composition of both samples was quite similar, the only difference was the relative content among their components.
RESUMO
Pólen de abelhas é uma mistura de pólens florais coletados pelas abelhas com ampla variação na sua composição. Investigação do pólen coletado pela abelha sem ferrão Scaptotrigona bipunctata levou a quatro agliconas de flavonóides: miricetina, dihidromiricetina, quercetina e isoramnetina. As estruturas foram estabelecidas a partir de dados espectroscópicos (NMR) das substâncias naturais.
Bee pollen is a mix of bee-collected floral pollens which varies widely in composition. Investigation of pollen collected by the stingless bee Scaptotrigona bipunctata yielded four flavonoid aglycones: myricetin, dihydromyricetin, quercetin and isorhamnetin. The structures were established from spectroscopic data (NMR) of the natural substances.
RESUMO
This paper describes recent results of design, synthesis and pharmacological evaluation of new N-heterocyclic functionalized N-acylhydrazone compounds, belonging to the 2-methyl-imidazolyl-3-acylhydrazone class (4a-e). These compounds were planned by applying the molecular simplification strategy to propose the structural modifications on the previously described functionalized imidazo [1,2-a]pyridine 3-acylhydrazone series (2), which presented an important analgesic profile. This new series (4) was synthesized in order to investigate the possible pharmacophoric contribution of the N-heteroaromatic ring and N-acylhydrazone moieties to the analgesic activity. Compounds 4a-b are the most potent antinociceptive agents from this series.