22338-69-8Relevant articles and documents
Preparation of antiproliferative terpene-alkaloid hybrids by free radical-mediated modification of ent-kauranic derivatives
Daelemans, Dirk,G?rbu, Vladilena,Kulci?ki, Veaceslav,Persoons, Leentje,Pruteanu, Elena,Renaud, Philippe,Ungur, Nicon
, (2021)
A convenient strategy for molecular editing of available ent-kauranic natural scaffolds has been developed based on radical mediated C–C bond formation. Iodine atom transfer radical addition (ATRA) followed by rapid ionic elimination and radical azidoalkylation were investigated. Both reactions involve radical addition to the exo-methylenic double bond of the parent substrate. Easy transformations of the obtained adducts lead to extended diterpenes of broad structural diversity and artificial diterpene-alkaloid hybrids possessing lactam and pyrrolidine pharmacophores. The cytotoxicity of selected diterpenic derivatives was examined by in vitro testing on several tumor cell lines. The terpene-alkaloid hybrids containing N-heterocycles with unprecedented spiro-junction have shown relevant cytotoxicity and promising selectivity indexes. These results represent a solid basis for following research on the synthesis of such derivatives based on available natural product templates.
Synthesis of Highly Functionalized Biologically Active Tetracyclic Diterpenoids from ent-Kaur-16-en-19-oic Acid under Modified Prévost-Woodward Reaction Conditions
Barba, A.,Garbuz, O.,Grinco, M.,Gulea, A.,Kulcitki, V.,Morarescu, O.,Ungur, N.
, p. 1931 - 1939 (2022/01/24)
Abstract: A procedure has been developed for the synthesis of highly functionalized tetracyclic diterpenoids from natural ent-kaur-16-en-19-oic acid under modified Prévost–Woodward reaction conditions. The reaction follows an unusual pathway which leads mainly to bromination or rearrangement products. The transforma-tion of ent-kaur-16-en-19-oic acid afforded a mixture of (16ZE)-17-bromo-ent-kaur-16-en-19-oic, (15R,16E)-17-bromo-15-acetoxy-ent-kaur-16-en-19-oic, (16S)-17-bromo-16-acetoxy-ent-kaur-19-oic, (15S)-15-acetoxy-ent-kaur-16-en-19-oic, and (15S)-15-hydroxy-ent-kaur-16-en-19-oic acids, the latter two being reported previously. The newly syn-thesized compounds were evaluated for their cytotoxicity against two cancer cell lines, HeLa and BxPC-3.
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.
Cytotoxic and apoptosis-inducing effect of ent-15-oxo-kaur-16-en-19-oic acid, a derivative of grandiflorolic acid from Espeletia schultzii
Ruiz, Yarimar,Rodrigues, Juan,Arvelo, Francisco,Usubillaga, Alfredo,Monsalve, Mariugenia,Diez, Nardy,Galindo-Castro, Ivan
, p. 432 - 438 (2008/09/18)
ent-Kaurenic acid and many natural derivatives of this diterpene are known to have interesting biological properties. ent-15-Oxo-kaur-16-en-19-oic acid can be easily obtained from grandiflorolic acid which was first isolated from Espeletia grandiflora. The present work describes the proapoptotic effect of ent-15-oxo-kaur-16-en-19-oic acid on the human prostate carcinoma epithelial cell line PC-3 as evidenced by the changes in the expression level of proteins associated with the execution and regulation of apoptosis. Cell viability was affected upon exposure to the compound, the IC50 were determined as 3.7 μg/ml, which is 4 times lower than that corresponding to a primary cell culture of fibroblasts (14.8 μg/mL). Through Western blot analysis, active forms of caspace-3 associated with the specific proteolysis of Poly(ADP-ribose) polymerase (PARP) were detected. Reduced levels of the antiapoptotic protein Bcl-2, as well as the appearance of internucleosomal DNA fragmentation, were also demonstrated. Thus, ent-15-oxo-kaur-16-en-19-oic acid may be a promising lead compound for new chemopreventive strategies, alone or in combination with traditional chemotherapy agents to overcome drug resistance in tumoral cells.
Ent-kaurenic Acid and Its Related Compounds from Glandular Trichome Exudate and Leaf Extracts of Polymnia sonchifolia
Kakuta, Hideo,Seki, Takuhiko,Hashidoko, Yasuyuki,Mizutani, Junya
, p. 1562 - 1564 (2007/10/02)
Yacon (Polymnia sonchifolia) leaves possess glandular trichomes on the surface.The exudate from the glandular trichome and the leaf are itself rich in ent-kaurenic acid (ent-kaur-16-en-19-oic acid).A kaurene derivative, 15-α-angeloyloxy-ent-kauren-19-oic
