Estudo fitoqu??mico e bioatividade de Diplotropis purpurea e Deguelia duckeana

• Author(s): Cursino, Lorena Mayara de Carvalho
• Date: 2016
• Origin: Oasisbr
• Subject(s): Potencial antic??ncer; Atividade antibacteriana; C??ncer; CI??NCIAS EXATAS E DA TERRA: QU??MICA
• Document Type: Doctoral thesis
• Language: Portuguese

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The present phytochemical study describes the isolation and identification of nine compounds from the roots dichloromethanic and branches hexanic extracts of Deguelia duckeana and three compounds from the leaves of Diplotropis purpurea hexanic extract, both species belonging to the Fabaceae family. The compounds from Deguelia duckeana were identified as stilbene (3,5,4???-trimethoxy-4- prenylstilbene), chalcones (4-methoxylonchocarpin and 4-methoxyderricidin), flavanones (5-hydroxy-4???,7-dimethoxy-6-prenylflavanone, 5-hydroxy-4???- methoxyisolonchocarpin), flavones (3???,4???-methylenedioxy-7-methoxyflavone, 3???,4???,7- trimethoxyflavone, racemoflavone) and one lignan (yangambin). Unprecedentedly, this study describes flavanone 5-hydroxy-4???,7-dimethoxy-6-prenylflavanone as a natural product at the literature. Other compounds as chalcone 4- methoxylonchocarpin, flavone racemoflavone and the lignan are also described by Deguelia without have been reported so far. The compounds of Diplotropis purpurea were identified as triterpenes lupeol, taraxerol and ??-amirin which are also first reported by Diplotropis, except lupeol. All the compounds were identified using 1H and 13C-NMR and LC/MS. In order to find active compounds, the extracts and isolated compounds from Deguelia duckeana were assayed for anticancer potential in neuroblastoma cells (SK-N-SH), among them one chalcone 4-hydroxylonchocarpin and one flavanone 4-hydroxyisolonchocarpin showed cytotoxicity by lactate dehydrogenase (LDH) assay. These two compounds also activated caspase-3, which indicate cell death via necrose and apoptosis. The other flavonoids induced phosphorylation of the eukaryotic elongation factor 2 (eEF2) and one flavone also induced AMP-activated protein kinase (AMPK). These results suggest that flavonoids have anticancer potential due to their effect on protein synthesis. Another biological activity examined in the present study was antibacterial activity of Diplotropis purpurea extracts and the most active was the methanolic extract from leaves, against three bacterial strains: Serratia marcescens (MIC at 250 mg/mL), Bacillus cereus (MIC at 1000 mg/mL) inhibiting 66% of bacterial growth in comparison with positive control and Providencia rettgeri (MIC at 250 mg/mL) with 69.5% of inhibition in comparison with positive control. The present study contributes to Deguelia duckeana and Diplotropis purpurea species chemical studies, due to their biological activities and description of six compounds on the genus are described by the first time at the literature. Among those compounds, one of them is also reported by the first time as a natural product.

O presente estudo fitoqu??mico descreve o isolamento e a identifica????o de nove subst??ncias obtidas dos extratos dicloromet??nico das ra??zes e hex??nico dos galhos de Deguelia duckeana e tr??s subst??ncias identificadas do extrato hex??nico das folhas de Diplotropis purpurea, ambas pertencentes ?? fam??lia Fabaceae. O estudo fitoqu??mico de Deguelia duckeana permitiu a identifica????o de estilbeno (3,5,4???- trimetoxi-4-prenilestilbeno), chalconas (4-metoxilonchocarpina e 4-metoxiderricidina), flavanonas (5-hidroxi-4???,7-dimetoxi-6-prenilflavanona e 5-hidroxi-4???-metoxiisolonchocarpina), flavonas (3???,4???-metilenodioxi-7-metoxiflavona, 3???,4???,7- trimetoxiflavona e racemoflavona) e uma lignana (iangambina). A flavanona 5- hidroxi-4???,7-dimetoxi-6-prenilflavanona merece destaque, pois est?? sendo descrita pela primeira vez na literatura, isolada de fonte natural. A chalcona 4- metoxilonchocarpina, a flavona racemoflavona e a lignana tamb??m est??o sendo descritas pela primeira vez em Deguelia. Do estudo fitoqu??mico de Diplotropis purpurea foram identificados tr??s triterpenos lupeol, taraxerol e ??-amirina. Com exce????o do lupeol, os demais triterpenos est??o sendo descritos pela primeira vez em Diplotropis. As subst??ncias foram identificadas por RMN de 1H e de 13C e CLAE/EM. Visando encontrar subst??ncias e extratos ativos, os mesmos foram analisados quanto ao potencial antic??ncer e atividade antibacteriana. Quanto ao potencial antic??ncer, o ensaio foi realizado em c??lulas de neuroblastoma humano (SK-N-SH) e verificou que a chalcona 4-hidroxilonchocarpina e a flavanona 4-hidroxiisolonchocarpina apresentaram citotoxicidade pelo teste da libera????o da enzima lactato desidrogenase (LDH) bem como a ativa????o da enzima caspase-3, o que infere dizer que essas duas subst??ncias possuem um mecanismo de necrose e posterior apoptose. Os demais flavonoides induziram a fosforila????o do fator de alongamento eucari??tico (eEF2) e uma flavona tamb??m induziu a fosforila????o da prote??na quinase ativada por AMP (AMPK). Estes resultados sugerem que os flavonoides apresentam potencial antic??ncer por apresentar atividade na s??ntese de prote??nas. Quanto ?? atividade antibacteriana dos extratos de Diplotropis purpurea foi observado que o extrato metan??lico das folhas mostrou-se mais ativo contra tr??s bact??rias: Serratia marcescens com CIM de 250 mg/mL, Bacillus cereus (CIM de 1000 mg/mL) com 66% de inibi????o em compara????o ao controle positivo e Providencia rettgeri (CIM de 250 mg/mL) apresentando 69,5% de inibi????o em compara????o ao controle positivo. O presente estudo destaca-se por contribuir significativamente para o conhecimento cient??fico das esp??cies Deguelia duckeana e Diplotropis purpurea, pois os estudos das atividades biol??gicas dessas esp??cies e a descri????o de seis subst??ncias est??o sendo relatadas pela primeira vez nos g??neros, sendo uma descrita pela primeira vez como produto natural