Structural Characterization and Biological Evaluation of 18‐Nor‐ent‐labdane Diterpenoids from Grazielia gaudichaudeana

Abstract

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent‐kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1H‐NMR chemical shifts of 18‐nor‐ent‐labdane (7–9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2 μg mL−1. Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor‐labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.

Neuroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastoma

“…Studies demonstrated that flavonoids act on glioma cells, including human GBM cells, affecting countless signaling pathways, including suppressing the activity of phosphatidylinositol 3-kinase (PI3K) [95], inhibiting the expression of extracellular regulatory matrix proteins and metalloproteinases [5], or activating Wnt/β-catenin signaling [96]. Studies describe the antitumor properties of flavonoids, such as jaceosidine [97], hispidulin [98], luteolin [99] and silibinin [100], with antiproliferative, cytotoxic, and cytostatic activities for the ethyl acetate fraction obtained from Grazielia gaudichaudeana [101], as shown for in vitro and in vivo models.…”

Advances on Natural Abietane, Labdane and Clerodane Diterpenes as Anti-Cancer Agents: Sources and Mechanisms of Action

“…The interest in studying labdane-type diterpenes was intensified in the past decades due to a wide range of bioactivities, including anti-inflammatory, anti-microbial, anti-mutagenic, and cytotoxic properties [ 92 , 93 , 94 ]. The family of labdane-type diterpenes constitutes a significant class of natural products, being composed of over 7000 compounds, which have been isolated from plants of several families, such as Asteraceae, Acanthaceae, Lamiaceae, Cistaceae, Cupressaceae, Pinaceae, Annonaceae, Caprifoliaceae, Zingiberaceae, Solanaceae, Apocynaceae, and Verbenaceae [ 95 ].…”

“…The analysis of structure–activity relationships suggests that a C-7 carbonyl group causes loss of activity (see uasdlabdanes A–C); a C-7 acetoxy group determines the best anti-proliferative effects (see uasdlabdane D vs. uasdlabdane E and F). Recently, Balbinot et al [ 95 ] investigated the chemical profile and the anti-proliferative activity of the aerial parts of Grazielia gaudichaudeana (Asteraceae). Fifteen compounds were identified and tested.…”

TOCSY, hydrogen decoupling and computational calculations to an unequivocal structural elucidation of a new sesquiterpene derivative and identification of other constituents from Praxelis sanctopaulensis

“…[3][4][5][6][7][8][9] Analysis of P. clematidea and P. pauciflora essential oil showed the presence of mono and sesquiterpenes. 9,10 Flavonoids have been isolated in great scale from Asteraceae, [11][12][13] four species of Eupatorium senso latu that occurs in Campos Gerais has been studied by our research group, [14][15][16][17] and in all of these species flavonoids have been found, especially in species belonging to the Chromolaena genus. 12,17 Chromolaena and Praxelis belong to the same subtribe, Praxelinae, and phylogenetic analysis of DNA sequence data showed a close relationship between these genera.…”