1721-69-3Relevant articles and documents
Molecular structure, in vitro anticancer study and molecular docking of new phosphate derivatives of betulin
B?benek, Ewa,Boryczka, Stanis?aw,Chrobak, Elwira,Jastrz?bska, Maria,Kadela-Tomanek, Monika,Kusz, Joachim,Latocha, Ma?gorzata,Marciniec, Krzysztof,Wrzalik, Roman
, (2021)
A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds 7a and 7b showed the highest activity against C-32 and SNB-19 cell lines. The IC50 values for 7a were 2.15 and 0.91 μM, and, for 7b, they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, 7a and 7b, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and KDEEP score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands 7a,b form stable complexes and the plateau phase started after 7 ns.
Amino(oxo)acetate moiety: A new functional group to improve the cytotoxicity of betulin derived carbamates
Heller, Lucie,Perl, Vincent,Wiemann, Jana,Al-Harrasi, Ahmed,Csuk, René
, p. 2852 - 2854 (2016)
While 3-O-acetylated betulin derivatives carrying a carbamate moiety at position C-28 are of rather low cytotoxicity for human tumor cell lines, the corresponding C-3 amino(oxo) acetates show good cytotoxicity. For example, an EC50 as low as 2.0 μM was found for (3β) 28-{[(hexylamino)carbonyl]oxy}lup-20(29)-en-3-yl amino(oxo)acetate (16) employing the ovarian cancer cell line A2780.
Selective inhibition of the interaction of C1q with immunoglobulins and the classical pathway of complement activation by steroids and triterpenoids sulfates
Bureeva, Svetlana,Andia-Pravdivy, Julian,Symon, Andrey,Bichucher, Anna,Moskaleva, Vera,Popenko, Vladimir,Shpak, Alexey,Shvets, Vitaly,Kozlov, Leonid,Kaplun, Alexander
, p. 3489 - 3498 (2007)
Since undesirable activation of the complement system through the classical pathway is associated with tissue damage and other pathologic proinflammatory consequences at ischemia/reperfusion injury, autoimmune diseases, and rejection of allo- and xenografts, creation of selective inhibitors of the classical pathway leaving the alternative pathway intact is of great importance. Classical pathway is triggered by binding of its recognizing unit, protein C1q, to a number of targets like antibodies, pentraxins, apoptotic cells, and others. In order to obtain inhibitors blocking the first step of the classical cascade, synthesis of sulfates of steroids (Δ5-3β-hydroxycholenic, Δ5-3β-hydroxyetiocholenic, deoxycholic, and cholic acids) and triterpenoids (betulin, 20,29-dihydro-20,29-dichloromethylenbetulin, betulinic, ursolic, and oleanolic acids) has been performed. Testing of the compounds in classical pathway inhibition assay has displayed derivatives of triterpenoid betulin (betulin disulfate and betulinic acid sulfate) to be the most potent inhibitors. Further studies of the two compounds established that their activity to inhibit the classical pathway had been due to their capability to block the interaction of C1q with antibodies. Betulin disulfate and betulinic acid sulfate have shown weak inhibition of the alternative route of activation, what makes them promising inhibitors for the selective suppression of the classical complement pathway at the earliest possible level as well as perspective agents for blocking the interaction of C1q with its other targets.
Zorina et al.
, (1966)
-
Dieterle,Leonhardt,Dorner
, p. 264,267 (1933)
-
New 30-substituted derivatives of pentacyclic triterpenes: preparation, biological activity, and molecular docking study
B?benek, Ewa,Boryczka, Stanis?aw,Chrobak, Elwira,Kadela-Tomanek, Monika,Latocha, Ma?gorzata,Marciniec, Krzysztof,Siudak, Szymon
, (2021)
A series of 30-substituted derivatives of 3,28-O,O′-diacetylbetulin 4-19 were prepared and assessed for anticancer activities in vitro against five human cancer cell lines (SNB-19, C-32, SKOV-3, MCF-7, and T47D). The triterpene 14, containing the butyryloxycarbonyl group at the C-30 position, showed the highest cytotoxicity, with IC50 values within the range of 1.24 to 6.03 μM towards applied cancer cells. The ADME study of the betulinines 4-19 were performed by determination of molecular weight (M), hydrogen bond acceptors (nHBA), hydrogen bond donors (nHBD), lipophilicity (cLogP), rotatable bonds (nROTB) and topological polar surface area (TPSA). Molecular docking was applied to examine the probable interaction between the new synthesized compounds and the Akt1 kinase. The analysis showed that triterpenes 13-16 formed numerous hydrophobic interactions inside the binding pocket of Akt1.
Antineoplastic Agents. 606. the Betulastatins
Pettit, George R.,Melody, Noeleen,Chapuis, Jean-Charles
, p. 458 - 464 (2018)
The medicinal potential of the plant pentacyclic triterpene betulin has generated long-term interest focused on various SAR research avenues. The present approach was based on producing further analogues (chimeras) arising from a studied modification of betulin bonded to the Dov-Val-Dil-Dap unit of the powerful anticancer drug dolastatin 10, which provided betulastatins 1 (7b), 2 (11b), 3 (16b), and 4 (18b). Betulastatin 1, 2, and 4 exhibited modest levels of cancer cell growth inhibition against six cancer cell lines. Betulastatin 3 proved to be the most potent cancer cell growth inhibitor (GI50 0.01 μg/mL) and seems worthy of further development, as the presumed mixture of anticancer mechanisms of action may prove to be useful.
ORGANIC PHOTOCHEMISTRY- PART II, PHOTOCHEMICAL SYNTHESIS OF THE NATURALLY OCCURING TRITERPENE LACTONE, 3β-HYDROXY LUPAN-28,13β-OLIDE
Nag, Swapan K.,Bose, Samarendra N.
, p. 2855 - 2856 (1989)
The photochemical synthesis of the title lactone was achieved by irradiation in the presence of Pb(IV) acetate alone or Pb(IV) acetate + calcium carbonate + iodine or mercuric oxide + iodine.Chiroptical measurements (CD) of this and other related lactones provided convincing evidence in support of the lactone ring structure.
Synthesis and cytotoxicity of triterpenoids derived from betulin and betulinic acid via click chemistry
Shi, Wei,Tang, Ning,Yan, Wei-Dong
, p. 159 - 169 (2015)
In this study, a series of triazole substituted betulin and betulinic acid derivatives was designed and synthesized via click chemistry at C-30 position. Eighteen target compounds were evaluated in vitro for their antitumor activities against leukemia cell-line HL-60. Seventeen compounds have not reported before. The cytotoxic experiment showed that most of betulinic acid derived triazoles have higher cytotoxic profile than betulinic acid. Among them, compound 30-[4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl] betulinic acid (7b) showed the best IC50 value (1.3 M) against leukemia cell-line HL-60 (eight- to ninefold higher potency than betulinic acid).
Activity of lupane triterpenoids from Maytenus species as inhibitors of nitric oxide and prostaglandin E2
Reyes, Carolina P.,Nunez, Marvin J.,Jimenez, Ignacio A.,Busserolles, Jerome,Alcaraz, Maria J.,Bazzocchi, Isabel L.
, p. 1573 - 1579 (2006)
In the present study, we report that three new lupane triterpenes (1-3), in addition to 16 known ones (4-19), were isolated from the root bark of Maytenus cuzcoina and the leaves of Maytenus chiapensis. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC, and HMBC). The natural compounds and derivatives 6a, 6b, 9a, and 9b have been tested for potential anti-inflammatory activity, and several compounds including 3-epicalenduladiol (2), 11α-hydroxy- glochidone (3), rigidenol (6), acetoxy-rigidenol (6a), 11α-acetoxy-30- chloro-3-oxo-lup-20(29)-ene (6b), betulin (9), 28-acetoxy-betulin (9a), epibetulin (12), epibetulinic acid (13), and betulonic acid (16) exhibited potent inhibitory effects on NO and prostaglandin E2 production in mouse macrophages (RAW 264.7) stimulated with bacterial endotoxin. The structure-activity relationship is discussed in detail.
Novel betulin derivatives inhibit IFN-γ and modulates COX-2 expression
Gnoato, Simone Cristina Baggio,Pitta, Ivan da Rocha,Pitta, Maira Galdino da Rocha,Gon?alves, Sayonara Maria Calado,Rêgo, Moacyr Jesus Barreto de Melo,Silva, Glória Najara
, p. 1702 - 1711 (2020)
Betulin (BE) is a pentacyclic triterpenes, obtained from natural sources and with several biological activities described, such as anti-tumoral and anti-inflammatory activities. The BE esterification at hydroxyl group (C-3 and C-28) resulted in five new ester derivatives with different numbers of carbons or halogens (chlorine and fluorine). Among these BE derivatives, two (2a e 2c) were able to significantly decrease IFN-g (*p = 0.0391; **p = 0.0156) and 2c modulated the expression of COX-2 better than Dexamethasone (DEXA). Regarding to cytotoxic assay, the best results were obtained for BE without modifications, with emphasis on tumoral cell lines Raji and MCF-7. The derivatives 2a and 2c showed immunomodulation activity (for the cytokines IFN-g). The presence of chorine in BE seems to be important for the ability of modulate COX-2 expression, since the ester chloride derivative 2c at 100 μM is more powerful inhibitor of COX-2 than DEXA.
Design and synthesis of novel betulin derivatives containing thio-/semicarbazone moieties as apoptotic inducers through mitochindria-related pathways
Bu, Ming,Han, Yinglong,Lin, Yu,Liu, Jicheng,Wang, Haijun,Wang, Jiafeng,Wang, Jing,Wu, Jiale,Zhang, Jie
, (2021/11/01)
Two new series of betulin derivatives with semicarbazone (7a–g) or thiosemicarbazone (8a–g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, 8f displayed the most potent cytotoxicity with an IC50 value of 5.86 ± 0.61 μM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound 8f could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound 8f may be used as a valuable skeleton structure for developing novel antitumor agents.
