18671-79-9Relevant academic research and scientific papers
Synthesis, cytotoxicity and antiplasmodial activity of novel ent-kaurane derivatives
Batista, Ronan,Garcia, Pablo A.,Castro, Maria Angeles,Miguel Del Corral, Jose M.,Speziali, Nivaldo L.,De P. Varotti, Fernando,De Paula, Renata C.,Garcia-Fernandez, Luis F.,Francesch, Andres,San Feliciano, Arturo,De Oliveira, Alaide B.
, p. 168 - 176 (2013/05/09)
This paper reports on the syntheses and spectrometric characterisation of eleven novel ent-kaurane diterpenoids, including a complete set of 1H, 13C NMR and crystallographic data for two novel ent-kaurane diepoxides. Moreover, the antineoplastic cytotoxicity for kaurenoic acid and the majority of ent-kaurane derivatives were assessed in vitro against a panel of fourteen cancer cell lines, of which allylic alcohols were shown to be the most active compounds. The good in vitro antimalarial activity and the higher selectivity index values observed for some ent-kaurane epoxides against the chloroquine-resistant W2 clone of Plasmodium falciparum indicate that this class of natural products may provide new hits for the development of antimalarial drugs.
Synthesis and induction of apoptosis signaling pathway of ent-kaurane derivatives
Hueso-Falcón, Idaira,Girón, Natalia,Velasco, Pilar,Amaro-Luis, Juan M.,Ravelo, Angel G.,Heras, Beatriz de las,Hortelano, Sonsoles,Estevez-Braun, Ana
experimental part, p. 1724 - 1735 (2010/04/29)
Thirty one ent-kaurane derivatives were prepared from kaurenoic acid (1), grandiflorenic acid (16), 15α-acetoxy-kaurenoic acid (26) and 16α-hydroxy-kaurenoic acid (31). They were tested for their ability to inhibit cell viability in the mouse leukemic macrophagic RAW 264.7 cell line. The most effective compounds were 12, 20, 21, and 23. These were selected for further evaluation in other human cancer cell lines such as Hela, HepG2, and HT-29. Similar effects were obtained although RAW 264.7 cells were more sensitive. In addition, these compounds were significantly less cytotoxic in non-transformed cells. The apoptotic potential of the most active compounds was investigated and they were able to induce apoptosis with compound 12 being the best inducer. The caspase-3, -8 and -9 activities were measured. The results obtained showed that compounds 12, 21, and 23 induce apoptosis via the activation of caspase-8, whereas compound 20 induces apoptosis via caspase-9. Immunoblot analysis of the expression of p53, Bax, Bcl-2, Bcl-xl, and IAPs in RAW 264.7 cells was also carried out. When cells were exposed to 5 μM of the different compounds, expression levels of p53 and Bax increased whereas levels of antiapoptotic proteins such as Bc1-2, Bc1-x1, and IAPs decreased. In conclusion, kaurane derivatives (12, 20, 21, and 23) induce apoptosis via both the mitochondrial and membrane death receptor pathways, involving the Bcl-2 family proteins. Taken together these results provide a role of kaurane derivatives as apoptotic inducers in tumor cells.
Fluorinated Kaurenoids. Part 2. Preparation of Methyl ent-17,17,17-Trifluorokaur-15-en-19-oate and ent-16,16-Difluoro-17-norkauran-19-oic Acid from Xylopic Acid
Cross, Brian E.,Erasmuson, Anton,Filippone, Paolino
, p. 1293 - 1297 (2007/10/02)
An attempt to convert methyl ent-16-oxo-17-norkauran-19-oate (3), derived from xylopic acid, into methyl ent-17,17-difluorokaur-16-en-19-oate failed.However, treatment of the norketone (3) with diethylaminosulphurtrifluoride (DAST) gave methyl ent-16,16-difluoro-17-norkauran-19-oate (5).The latter afforded the corresponding acid (4) which was active as a growth promoter in a dwarf-rice bioassay.Treatment of methyl deacetylxylopate (18) with DAST, followed by cleavage of the terminal methylene group, yielded methyl ent-15-fluoro-16-oxo-17-norkauran-19-oate (15), which on reaction with dibromodifluoromethane and tris(dimethylamino)phosphine gave, not the expected 17,17-difluoro-olefin (19), but methyl ent-17,17,17-frifluorokaur-15-en-19-oate (28) in poor yield.Reduction of methyl xylopate with di-imide gave the 16β-methyl compound (24) stereospecifically.The latter was readily converted into methyl 15-oxokauranoate (26), but steric hindrance prevented the reaction of the oxo-group with DAST to give the 15,15-difluoride, under normal reaction conditions; using a much longer reaction time a trace of the gem-difluoride was formed.During reduction of the dithiocarbonate (27) of methyl deacetylxylopate with tri-n-butyltin hydride into the isomeric methyl kaurenoates (8) and (31), the 17-thiol ester (32) was also formed by a sigmatropic rearrangement.
