125225-30-1Relevant articles and documents
Synthesis and characterization of some new 1,2,3-thiadiazole and 1,2,3-selenadiazole triterpene derivatives from allobetulone and 2-oxoallobetulin
Dinh Ngoc, Thuc
, p. 1665 - 1671 (2020)
The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives from triterpenoid ketones has been investigated via the corresponding semicarbazones. The intermediates 5, 8 have also been isolated, separated and their structures identified. The Hurd–Mori reaction and Lalezari method have been applied to synthesize a series of new substances 6 and 7. The regioselectivity of the functionalization mostly was centered at the C-3 position for the products 9 and 10. The structures of these compounds were confirmed by 2D-NMR spectroscopy.
Synthesis and cytotoxic activity of triterpenoid thiazoles derived from allobetulin, methyl betulonate, methyl oleanonate, and oleanonic acid
Borkova, Lucie,Adamek, Richard,Kalina, Petr,Dra?ar, Pavel,Dzubak, Petr,Gurska, Sona,Rehulka, Jiri,Hajduch, Marian,Urban, Milan,Sarek, Jan
, p. 390 - 398 (2017)
A total of 41 new triterpenoids were prepared from allobetulone, methyl betulonate, methyl oleanonate, and oleanonic acid to study their influence on cancer cells. Each 3-oxotriterpene was brominated at C2 and substituted with thiocyanate; subsequent cyclization with the appropriate ammonium salts gave N-substituted thiazoles. All compounds were tested for their in vitro cytotoxic activity on eight cancer cell lines and two non-cancer fibroblasts. 2-Bromoallobetulone (2b) methyl 2-bromobetulonate (3b), 2-bromooleanonic acid (5b), and 2- thiocyanooleanonic acid (5c) were best, with IC50 values less than 10 mm against CCRF-CEM cells (e.g., 3b: IC50=2.9 μm) as well as 2'-(diethylamino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5 f, IC50=9.7 μm) and 2'-(N-methylpiperazino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5k, IC50=11.4 μm). Compound 5c leads to the accumulation of cells in the G2 phase of the cell cycle and inhibits RNA and DNA synthesis significantly at 1xIC50. The G2/M cell-cycle arrest probably corresponds to the inhibition of DNA/RNA synthesis, similar to the mechanism of action of actinomycin D. Compound 5c is new, active, and nontoxic; it is therefore the most promising compound in this series for future drug development. Methyl 2-bromobetulonate (3b) and methyl 2-thiocyanometulonate (3c) were found to inhibit nucleic acid synthesis only at 5xIC50. We assume that in 3b and 3c (unlike in 5c), DNA/RNA inhibition is a nonspecific event, and an unknown primary cytotoxic target is activated at 1xIC50 or lower concentration.
Antineoplastic agents. 595. structural modifications of betulin and the X-ray crystal structure of an unusual betulin amine dimer1
Pettit, George R.,Melody, Noeleen,Hempenstall, Frank,Chapuis, Jean-Charles,Groy, Thomas L.,Williams, Lee
, p. 863 - 872 (2014)
The lupane-type triterpene betulin (1) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence 7 11 12 was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the 11 and 13/1417 conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer 12 and intermediate 25 are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for 4, 8, 9, 15/16, 19, 20, 24, and 26, which further defines the utility of the betulin scaffold.
Antiproliferative effect of mitochondria-targeting allobetulin 1,2,3-triazolium salt derivatives and their mechanism of inducing apoptosis of cancer cells
Wang, Rui,Li, Yang,Dehaen, Wim
, (2020)
Herein we report the targeting effect of 1,2,3-triazolium salt derivatives of allobetulin on cancer cells mitochondria and their antiproliferative mechanism. A series of allobetulin derivatives with 1,2,3-triazolium positively charged units was designed and synthesized by multi-component triazolization reaction and alkylation. The screening of cytotoxicity showed that all the 1,2,3-triazolium salt derivatives of allobetulin displayed better cytotoxicity than the parent compound allobetulin and commercial anticancer drugs gefitinib. The most potent compound 4q showed strong anticancer activity, especially for Eca-109 cells. Compound 4n showed the strongest inhibitory effect on SGC-7901 cells. Further anticancer mechanism studies indicated that compounds 4n and 4q induced apoptosis through the mitochondrial pathway. Compounds 4n and 4q acted on mitochondria to cause an increase in intracellular reactive oxygen species and a change in the level of apoptosis-related protein (Bcl-2, Bcl-xL and Bax), which resulted in a decrease in membrane potential and activation of caspase family to induce cancer cells apoptosis. Meanwhile, compounds 4n and 4q could induce cancer cells apoptosis by arresting the cell cycle. Due to the strong cytotoxicity of compounds 4n and 4q, they are expected to become new anticancer agents and deserve further study.
Synthesis of betulin derivatives with solid supported reagents
Lavoie,Pichette,Garneau,Girard,Gaudet
, p. 1565 - 1571 (2001)
Betulin-allobetulin transformation is effected with ferric nitrate or ferric chloride adsorbed onto silica gel or alumina, in excellent yields. In addition, allobetulin can be converted to allobetulone with silica adsorbed ferric nitrate or to 19β,28-epoxy-A-neo- 18α-olean-3(5)-ene and 19β,28-epoxy-A-neo-5β-methyl-25-nor-18α-olean-9-ene with silica or alumina adsorbed ferric chloride.
Allobetulin derived seco-oleananedicarboxylates act as inhibitors of acetylcholinesterase
Heller, Lucie,Schwarz, Stefan,Obernauer, Anja,Csuk, René
, p. 2654 - 2656 (2015)
Ring opening of allobetulone gave either seco-acid 8 or di-acid 4. These acids were converted into esters that were screened by Ellman's assay. A dibutenylester of low cytotoxicity (NIH 3T3 murine embryonic fibroblasts) was shown to be a good mixed-type inhibitor (Ki = 3.39, Ki′ = 2.26 μM) for acetylcholinesterase.
Reaction of 3-acetoxy-(2,3),(19β,28)-diepoxyoleanane with cyclic and linear amines
Tolmacheva,Shelepen'Kina,Shashkov,Grishko,Glushkov,Tolstikov
, p. 153 - 158 (2007)
A mixture of diastereomeric 3-acetoxy-(2,3),(19β,28)-diepoxyoleananes was prepared via reaction of 3-acetoxy-19β,28-epoxyolean-2-ene with m-chloroperbenzoic acid. Directed rearrangement of these formed 2β-acetoxy-19β,28-epoxyolean-3-one whereas heating of them in amines produced oleanane-type enamines.
