25488-53-3Relevant academic research and scientific papers
Synthesis of 3-O-acyl/3-benzylidene/3-hydrazone/3-hydrazine/17- carboxyacryloyl ester derivatives of betulinic acid as anti-angiogenic agents
Mukherjee, Rama,Jaggi, Manu,Rajendran, Praveen,Srivastava, Sanjay K.,Siddiqui, Mohammad J. A.,Vardhan, Anand,Burman, Anand C.
, p. 3169 - 3172 (2004)
New 3-O-acyl, 3-benzylidene, 3-hydrazone, 3-hydrazine, 17-carboxyacryloyl ester derivatives of betulinic acid (2-6, 8-11, 13, 17, 18, 21, and 22) were synthesized and evaluated in vitro for anti-angiogenic activity on endothelial cell cytotoxicity, specificity, and tube-formation ability. All derivatives reported here showed IC505010) in some cases. Compounds 10, 17, and 18 have shown 20%, 32%, and 48% reduction in TLS, respectively, and were found better than betulinic acid (1). We have shown that 20,29-dihydrobetulinic acid derivatives have better anti-angiogenic activity as compared to betulinic acid or its other derivatives.
Synthesis and evaluation of biological activity of the auaternary ammonium salts of lupane-, oleanane-, and ursane-type acids
Biedermann, David,Eignerova, Barbara,Hajduch, Marian,Sarek, Jan
, p. 3839 - 3848 (2010)
The anticancer properties of the derivatives of natural pentacyclic triterpenoids have received much attention recently. Here we present the preparation and the evaluation of the anticancer activity of a novel group of derivatives: quaternary ammonium esters. The esters were synthesized by quaternization of the respective 2-bromoethyl esters of betulinic, dihydrobetulinic, platanic, oleanolic, ursolic, and 3-acetoxy-21-oxolup-18-en- 28-oic acids with common low-molecular-weight tertiary amines, namely trimethylamine, triethylamine, pyridine, and triethanolamine. However, the desired quaternary salts were obtained only from trimethylamine, triethylamine, and pyridine. In case of the reaction with triethanol?amine the elimination of one of the 2-hydroxyethyl groups occurred and only tertiary amines were formed. Most of the prepared compounds showed significant in vitro cytotoxic activity on the CEM T-lymfoblastic leukaemia cell line. Three of the six selected compounds {2-(triethylammonio)ethyl 3-hydroxylup-20(29)-en-28-oate bromide, 2-(triethylammonio)ethyl 3b-hydroxylupan-28-oate bromide and 2-[bis(2-hydroxyethyl)amino]ethyl 3-hydroxylupan-28-oate] exhibited strong cytotoxic activity on a panel of ten cell lines, including drug resistant. Georg Thieme Verlag Stuttgart · New York.
Pentacyclic triterpene compound, preparation method thereof, pharmaceutical composition and use of pharmaceutical composition
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Paragraph 0077; 0078; 0079, (2019/04/14)
The invention discloses a pentacyclic triterpene compound, a preparation method thereof, a pharmaceutical composition and use of the pharmaceutical composition. The structure of the pentacyclic triterpene compound is represented by a general formula I, wherein each substituent in the formula is described in the specification and the claims. The pentacyclic triterpene compound has an effective antagonistic effect to an FXR receptor. Compared with certain existing natural FXR antagonists, the pentacyclic triterpene compound is relatively rich in natural sources, and a synthetic method of the pentacyclic triterpene compound is relatively simple and convenient.
Synthetic Analogues of Betulinic Acid as Potent Inhibitors of PS1/BACE1 Interaction to Reduce Aβ Generation
Zhang, Chenlu,Wang, Xiaoyin,Cui, Jin,Li, Xiaohang,Zhang, Yangming,Wang, Xin,Gu, Haifeng,Li, Wei,Xie, Xin,Zhao, Jian,Pei, Gang,Nan, Fajun
, p. 103 - 112 (2017/02/05)
The lupane-type triterpenoids are endowed with a wide range of biological activities such as antiviral, anti-inflammatory and anticancer activity. We describe here its potential application in Alzheimer's disease (AD) treatment as an inhibitor of PS1/BACE1 interaction. 3-α-Akebonoic acid, which emanated from a high throughput screening (HTS), was discovered to interfere with PS1/BACE1 interaction and reduce amyloid β-protein (Aβ) production. In view of the limited source, we instead used naturally rich betulinic acid (compound 2) as starting material for lead optimization and a focused library of its derivatives was constructed to gain a better understanding of the structure activity relationship (SAR) of triterpenoid-type inhibitor of PS1/BACE1 interaction. Compound 22 was finally chosen as the most potent PS1/BACE1 interaction inhibitor, which reduced Aβ generation effectively.
Synthesis of cytotoxic 2,2-difluoroderivatives of dihydrobetulinic acid and allobetulin and study of their impact on cancer cells
Borkova, Lucie,Jasikova, Lucie,Rehulka, Jiri,Frisonsova, Katerina,Urban, Milan,Frydrych, Ivo,Popa, Igor,Hajduch, Marian,Dickinson, Niall J.,Vlk, Martin,Dzubak, Petr,Sarek, Jan
, p. 482 - 490 (2015/05/13)
In this article, we describe the preparation and cytotoxic properties of a small focused library of lupane and 18plusmn;-oleanane triterpenoids that contain a combination of two structural motifs known to enhance the biological activities. First, we introduced two fluorine atoms to position 2 of the skeleton. Second, we synthesized a set of hemiester prodrugs, which were intended to increase the solubility and activity. Starting from betulin, we obtained two hydroxyketones (derivatives of dihydrobetulinic acid and allobetulin) and their fluorination using DAST provided 2,2-difluoro-3-oxo-compounds as the main products. Then the 3-oxo group in each derivative was reduced by NaBH4 to obtain 32-hydroxy compounds suitable for modifying by various hemiesters. We prepared 21 compounds, 11 of them new, their cytotoxicity was tested on T lymphoblastic leukemia CCRF-CEM cells first and the most active derivatives were selected for screening on another six tumor and two non-tumor cell lines. All of them showed selectivity against cancer lines with therapeutic index between 2 and 8. All hemiesters had activity in the same range as the free hydroxyl derivatives and they would be suitable prodrugs for future in vivo experiments. Interestingly, all hemiesters of 2,2-difluorodihydrobetulonic acid had higher activity against p53 knock-out p53g'/g' cancer cell line than against the non-mutated analog. In active derivatives, the cell cycle was analyzed by flow cytometry and several compounds slowed down cell cycle progression through G0/G1 or S-phase.
C-28 AMIDES OF MODIFIED C-3 BETULINIC ACID DERIVATIVES AS HIV MATURATION INHIBITORS
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Page/Page column 198, (2011/12/14)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, modified C-3 and C-28 betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors. These compounds are useful for the treatment of HIV and AIDS.
An amphiphilic conjugate approach toward the design and synthesis of betulinic acid-polyphenol conjugates as inhibitors of the HIV-1 gp41 fusion core formation
Liu, Yan,Ke, Zhuofeng,Wu, Kwok Yiu,Liu, Shuwen,Chen, Wen-Hua,Jiang, Shibo,Jiang, Zhi-Hong
scheme or table, p. 1654 - 1664 (2012/01/06)
Exploration of potent inhibitors of the HIV-1 gp41 fusion core formation is a promising strategy to discover small-molecule HIV-1 entry inhibitors for the treatment of HIV-1 infection. In this paper, a series of novel betulinic acid-polyphenol conjugates was designed, guided by molecular modeling of the binding of betulinic acid (BA) and phenolic galloyl/caffeoyl groups in the groove on the gp41 N-terminal heptad repeat (NHR) trimeric coiled coil. These conjugates were synthesized via conjugation of galloyl and caffeoyl groups with BA at the C-28 position. Their inhibitory activities of HIV gp41 six-helix bundle (6-HB) formation between the NHR peptide N36 and the C-terminal heptad repeat (CHR) peptide C34 were evaluated with size-exclusion HPLC. Conjugates bearing a galloyl group were found to exhibit four to sixfold higher inhibitory activities than that of parent compound BA, suggesting that they may be exploitable as HIV-1 fusion/entry inhibitors targeting gp41. The docking study on BA and its derivatives suggests that hydrophobic and hydrogen-bonding pockets exist in the groove of the gp41 NHR trimeric coiled coil and that a potent inhibitor should have amphiphilic structures to cooperatively interact with both pockets. This possibility was explored by incorporating both lipophilic and hydrophilic groups into the conjugates in a well-defined orientation to bind with both pockets in the gp41 NHR-trimer.
Structure - Activity relationship study of betulinic acid, a novel and selective TGR5 agonist, and its synthetic derivatives: Potential impact in diabetes
Genet, Cédric,Strehle, Axelle,Schmidt, Céline,Boudjelal, Geoffrey,Lobstein, Annelise,Schoonjans, Kristina,Souchet, Michel,Auwerx, Johan,Saladin, Régis,Wagner, Alain
experimental part, p. 178 - 190 (2010/04/30)
We describe here the biological screening of a collection of natural occurring triterpenoids against the G protein-coupled receptor TGR5, known to be activated by bile acids and which mediates some important cell functions. This work revealed that betulinic (1), oleanolic (2), and ursolic acid (3) exhibited TGR5 agonist activity in a selective manner compared to bile acids, which also activated FXR, the nuclear bile acid receptor. The most potent natural triterpenoid betulinic acid was chosen as a reference compound for an SAR study. Hemisyntheses were performed on the betulinic acid scaffold, and we focused on structural modifications of the C-3 alcohol, the C-17 carboxylic acid, and the C-20 alkene. In particular, structural variations around the C-3 position gave rise to major improvements of potency exemplified with derivatives 18 dia 2 (RG-239) and 19 dia 2. The best derivative was tested in vitro and in vivo, and its biological profile is discussed.
Synthesis and cytotoxic activity of heterocyclic ring-substituted betulinic acid derivatives
Kumar, Vivek,Rani, Nidhi,Aggarwal, Pawan,Sanna, Vinod K.,Singh, Anu T.,Jaggi, Manu,Joshi, Narendra,Sharma, Pramod K.,Irchhaiya, Raghuveer,Burman, Anand C.
scheme or table, p. 5058 - 5062 (2009/05/07)
A new series of betulinic acid derivatives have been synthesized by introducing heterocyclic ring between C-2 and C-3 positions of betulinic acid. Further modifications were also carried out by reduction of C-20(29) unsaturated bond and substitution of C-28 carboxyl group by ester and amide linkage to enhance the selectivity. Compound 11 resulted in IC50 of 2.44, 2.5, and 2.7 μg/ml on MIAPaCa, PA-1, and SW620 cancer cell lines, respectively. Compound 38 resulted in IC50 of 0.67 μg/ml on MIAPaCa cell line.
triterpenoid pyrazines and benzopyrazines with cytotoxic activity
Urban, Milan,Sarek, Jan,Kvasnica, Miroslav,Tislerova, Iva,Hajduch, Marian
, p. 526 - 532 (2008/02/11)
Twelve lupane, 18α-oleanane, and des-E-lupane derivatives (1a-5b) were either extracted from natural sources or synthesized from betulinic acid (1a) and betulin (2). Compounds 1b, 1c, 3b, 3c, 4b, 4c, 5a, and 5b were then used as starting materials for further synthesis of a series of pyrazines and benzopyrazines (6a-18); 20 of them are new (6a-6c, 7a-7d, and 10a-18). Activity of pyrazine 6a against the T-lymphoblastic leukemia cell line CEM encouraged us to synthesize several new esters (6b-6d) to study structure-activity relationships with respect to substitution of the carboxyl group at position 28. The synthesized compounds were tested for cytotoxicity against a variety of cancer cell lines of different histogenetic origin, and the results were compared with cytotoxicity of the known starting compounds. Significant cytotoxic activity against A 549, K 562, and multidrug-resistant K 562-tax cell lines was found in pyrazines 6a, 6d, and 6e.
