Phytochemical Study of Two Species of Hyptis from Northeast of Brazil: Hyptis carvalhoi Harley and Hyptis crassifolia Mart. ex Benth. and Anticancer Activity of the Isolated Compound.

• Autor(a) principal: Karisia Sousa Barros de Lima
• Data de Publicação: 2014
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
• Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13329
• topic: Hyptis crassifolia; Hyptis carvalhoi; Diterpenos abietanos; Atividade anticÃncer; Abietane diterpenes; Anti-cancer activity; QUIMICA DOS PRODUTOS NATURAIS

This work describes the phytochemical investigation of two specimens of Hyptis: H. carvalhoi Harley and H. crassifolia Mart. ex Benth., whose purpose is to investigate northeastern Brazil plants of the Hyptis genus, in the search for bioactive compounds, especially with anticancer activity. The chemical analysis of both species resulted in the isolation and characterization of 10 substances for H. crassifolia and 12 substances for H. carvalhoi. Of the ethanol extract from roots of H. crassifolia were isolated nine diterpenes and the known triterpene betulinic acid. Of the nine diterpenes, four are abietanes: 12-hydroxy-8,11,13-abietatriene, 12-hydroxy-8,11,13-abietatrie-7-one, 11,12,15-tri-hydroxy-8,11,13-abietatrien-7-one and 6α,11,12,15-tetra-hydroxy-8,11,13-abietatrien-7-one, from which 11,12,15-tri-hydroxy-8,11,13-abietatrien-7-one is being reported for the first time in the literature as a new natural abietane diterpene and the 6α,11,12,15-tetra-hydroxy-8,11,13-abietatrien-7-one is unknow. Three have rearranged abietanes skeletons: 11,12,14,16-tetra-hydroxy-17 -abeo-abieta-8,11,13-trien-7-one, 11,12,16-tri-hydroxy-17 -abeo-abieta-8,11,13-trien-7-one and (16S)-12,16-epoxy-11,14-di-hydroxy-17 -abeo-abieta-8,11,13-trien-7-one, from which the 11,12,16-tri-hydroxy-17 -abeo-abieta-8,11,13-trien-7-one is unknown, and to the (16S)-12,16-epoxy-11,14-di-hydroxy-17 -abeo-abieta-8,11,13-trien-7-one is proposed a revision of the 1H and 13C NMR data previously reported in the literature. Two known labdane diterpenes: 11-oxomanoyl oxide and 11β-hydroxymanoyl oxide were also isolated. From the hexane extract of the roots of H. carvalhoi were isolated ten diterpenes, one compound from a mixed biosynthesis, 3β-[4â-acetoxyangeloiloxy]-tremetone, not yet reported for the Lamiaceae, and betulinic acid, a chemotaxonomic marker for the genus Hyptis. Of the ten diterpenes, five are abietane: 12-hydroxy-8,11,13-abietatrien-20-al, 8,11,13-abietatrien-12,20-diol, 11-hydroxy-12-metoxy-8,11,13-abietatrien-10-oic acid, 12-hydroxy-8,11,13-abietatrien-10-oic acid and 12-hydroxy-8,11,13-abietatriene, an unknown nor-diterpene, with a 20-nor-icetexane skeleton identified as 8(7),10(7)-di-epoxy-12-hydroxy-20-nor-8,11,13-abietatriene, a pimarane diterpene, 11-ketosandaracopimar-15-en-8β-ol, unknow in the Lamiaceae and three tanshinones: 7β-hydroxy-11,14-di-oxoabieta-8,13-diene, 7,12-di-hydroxy-8,12-abietadien-11,14-di-oxo-20-al and 7α-hydroxy-11,14-dioxoabieta-8,13-diene, from which the last is unknown. All compounds were isolated using successive chromatographic purification steps, including HPLC, and structural determination was performed by mean of spectroscopic techniques such as HRMS, IR, 1H and 13C NMR, including uni and bidimensional pulse sequences, and comparison with data from the literature. Among the isolated compounds, eighteen have been tested for cell-growth inhibition activity against several human cancer cell lines, and ten showed activity. From the compounds isolated from H. crassifolia, 12-hydroxy-8,11,13-abietatriene and 11,12,14,16-tetra-hydroxy-17 -abeo-abieta-8,11,13-trien-7-one showed a moderate cytotoxic activity, while 12-hydroxy-8,11,13-abietatrie-7-one exhibited a moderate, but selective activity against leukemia cell line. All diterpenes isolated from H. carvalhoi exhibited cytotoxic activity, but 7,12-di-hydroxy-8,12-abietadien-11,14-di-oxo-20-al, after 72 hours of incubation, showed IC50 values ranging from 3.91 to 32.01 μM in colon tumor (HCT-116) and leukemic (HL-60) cells, respectively. Its possible mechanism of action was then studied.