4481-62-3Relevant academic research and scientific papers
A convergent synthesis of novel alkyne–azide cycloaddition congeners of betulinic acid as potent cytotoxic agent
Dangroo, Nisar A.,Singh, Jasvinder,Rath, Santosh K.,Gupta, Nidhi,Qayum, Arem,Singh, Shashank,Sangwan, Payare L.
, p. 1 - 12 (2017)
In an endeavour to develop potent anti-tumor agents from betulinic acid (BA), a series of C-28 derived 1,2,3-triazolyl derivatives were designed and synthesized by employing Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition reaction. All the derivatives were evaluated for cytotoxic activity by MTT assay against five different human cancer cell lines: lung (A549), colon (HCT116), prostate (PC3), pancreatic (MIA PaCa-2) and breast (T47D). The data revealed that compounds 11c, 11d, 11g, 11h and 13a possess most promising cytotoxic potential. The compound 11h was one of the most active compounds, with IC50 values in the range of 4–6?μM against all the five cancer cell lines. The results of this study suggested that derivatives with free –OH (11c, 11d and 11g) and free –COOH (11h and 13a) substitutions in the triazole moiety introduced at the C-28 position significantly improved the anti-tumor activity and may be the favourable position to synthesize potent anticancer leads from BA. Introduction of a non polar alkyl groups at C-28 position (10, 12 and 14) resulted in the significant loss of the activity. Further, DAPI staining, ROS generation and wound healing experiments revealed that compound 11h induces apoptosis in HCT-116 cells.
Autoxidation Products of Betulonaldehyde
Ayers, Sloan,Benkovics, Tamas,Marshall, Jonathan,Tan, Yichen,Strotman, Neil A.,Kiau, Susanne
, p. 2758 - 2761 (2016)
Three major degradation products resulted from the exposure of betulonaldehyde (1) to air in solution at room temperature. From HRMS and NMR data, the products, which were isolated by preparative supercritical fluid chromatography (SFC), were identified a
Synthesis of novel lupane triterpenoid-indazolone hybrids with oxime ester linkage
Khlebnicova, Tatyana S.,Shishkina, Svetlana V.,Zicāne, Daina,Piven, Yuri A.,Tetere, Zenta,Baranovsky, Alexander V.,Rāvi?a, Irisa,Lakhvich, Fedor A.,Kumpi??, Viktors,Rijkure, Inese,Mieri?a, Inese,Peipi??, Uldis,Turks, Māris
, p. 77 - 89 (2017)
An efficient protocol for the synthesis of novel lupane triterpenoid-indazolone hybrids with oxime ester linkage has been developed from naturally accessible precursor betulin. For the first time a series of betulonic acid-indazolone hybrids have been synthesized via an acylation of corresponding 6,7-dihydro-1H-indazol-4(5H)-one oximes with betulonic acid chloride. Diastereoselective reduction of the obtained betulonic acid conjugates with NaBH4resulted in a formation of betulinic acid-indazolone hybrids in excellent yields. The configuration of the key compounds has been fully established by X-ray and 2D NMR analysis.
Synthesis of heterocycle-modified betulinic acid derivatives as antitumor agents
Cui, Hai-Wei,He, Yuan,Wang, Jinhua,Gao, Wei,Liu, Ting,Qin, Min,Wang, Xue,Gao, Cheng,Wang, Yan,Liu, Ming-Yao,Yi, Zhengfang,Qiu, Wen-Wei
, p. 240 - 248 (2015)
Abstract A series of novel heterocycle-modified betulinic acid (BA) derivatives were synthesized and investigated for their activity against the growth of eight non-drug resistant and one multidrug-resistant tumor cell line using a sulforhodamine B (SRB) assay. The most active compound 17 showed an average IC50 1.19 μM, which was about 20 times more potent than the lead compound BA. It is amazing that for most synthetic saturated N-heterocycle derivatives, MCF-7/ADR was the most sensitive tumor cells, especially 17 showed the most potent antitumor activity (IC50 = 0.33 μM) on this multidrug-resistant tumor cell line, that was 117 times more potent than BA. Most of the tested compounds displayed less toxic on human fibroblasts (HAF) in comparison with the tumor cell lines. The cytometry and transwell migration assays were used to test the ability of 17 to induce apoptosis and inhibit metastasis on tumor cell lines respectively.
Novel Betulinic Acid-Nucleoside Hybrids with Potent Anti-HIV Activity
Wang, Qiang,Li, Yujiang,Zheng, Liyun,Huang, Xiaowan,Wang, Yanli,Chen, Chin-Ho,Cheng, Yung-Yi,Morris-Natschke, Susan L.,Lee, Kuo-Hsiung
, p. 2290 - 2293 (2020)
Novel betulinic/betulonic acid-nucleoside hybrids were synthesized as possible new anti-HIV agents. Among the synthesized hybrids, two compounds were highly effective against HIV. Compared with AZT and DSB, compounds 10a (IC50= 0.0078 μM, CC50= 9.6 μM) and 10b (IC50= 0.020 μM, CC50= 23.8 μM) showed more potent or equipotent, respectively, anti-HIV activity but displayed lower cytotoxicity.
Optimization of invasion-specific effects of betulin derivatives on prostate cancer cells through lead development
H?rm?, Ville,Haavikko, Raisa,Virtanen, Johannes,Ahonen, Ilmari,Schukov, Hannu-Pekka,Alakurtti, Sami,Purev, Enkhee,Rischer, Heiko,Yli-Kauhaluoma, Jari,Moreira, Vania M.,Nees, Matthias,Oksman-Caldentey, Kirsi-Marja
, (2015)
The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D) growth conditions using non-transformed prostate epithelial cells (EP156T), an androgen-sensitive prostate cancer cell line (LNCaP), and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D) growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.
Synthesis and anti-HCV entry activity studies of β-cyclodextrin- pentacyclic triterpene conjugates
Xiao, Sulong,Wang, Qi,Si, Longlong,Shi, Yongying,Wang, Han,Yu, Fei,Zhang, Yongmin,Li, Yingbo,Zheng, Yongxiang,Zhang, Chuanling,Wang, Chunguang,Zhang, Lihe,Zhou, Demin
, p. 1060 - 1070 (2014)
In our previous studies, oleanolic acid (OA) and echinocystic acid (EA), isolated from Dipsacus asperoides, were found to have anti-HCV entry properties. The major issue for members of this type of triterpene is their low water solubility. In this study, a series of new water-soluble triazole-bridged β-cyclodextrin (CD)-pentacyclic triterpene conjugates were synthesized via click chemistry. Thanks to the attached β-CD moiety, all synthesized conjugates showed lower hydrophobicity (Alog P) than their parent compounds. Several conjugates exhibited moderate anti-HCV entry activity. With the exception of per-O-methylated β-CD-pentacyclic triterpene conjugates, all other conjugates showed no cytotoxicity based on an alamarBlue assay carried out with HeLa, HepG2, MDCK, and 293T cells. More interestingly, the hemolytic activity of these conjugates disappeared upon the introduction of β-CDs. Easy access to such conjugates that combine the properties of β-CD and pentacyclic triterpenes may provide a way to obtain a new class of anti-HCV entry inhibitors. An awesome CD collection: A series of water-soluble triazole-bridged β-cyclodextrin (CD)-pentacyclic triterpene conjugates were synthesized, and their hydrophobicity, anti-HCV entry activities, and toxicity were studied. Easy access to such conjugates may provide a way to obtain a new class of anti-HCV entry inhibitors.
Rhodamine B-based fluorescent probes for molecular mechanism study of the anti-influenza activity of pentacyclic triterpenes
Chen, Yingying,Li, Man,Ma, Wenxiao,Ran, Fuxiang,Xiao, Sulong,Yuan, Lan,Zhang, Lihe,Zhou, Demin
, (2020)
The antiviral activity of pentacyclic triterpenes has attracted increasing attention. However, the detailed antiviral mechanism remains fully unclear. In the present study, four C28 or C30 modified pentacyclic triterpene probes via conjugating with rhodamine B were designed and synthesized, and their anti-influenza virus activity was evaluated. The results indicated that two compounds 14 and 23 showed significant antiviral activity to influenza A/WSN/33 (H1N1) virus in Madin-Darby canine kidney (MDCK) cells with IC50 values of 8.36 and 8.24 μM, respectively. The mechanism of action studies of representative probe 23 indicated that it could inhibit the membrane fusion by binding with influenza virus hemagglutinin (HA), and the apparent dissociation constant (KD) value for probe 23-HA interaction was successfully evaluated (1.78 × 10?5 M) using surface plasmon resonance spectroscopy. In addition, the subcellular localization of probe 23 in MDCK cells was determined by confocal microscopy and flow cytometry, and the results suggested that fluorescent probe 23 was rapidly taken up in MDCK cells and accumulated in cytoplasm, but no antiviral activity was observed after its entry into cells. The present study further confirmed our previous finding that pentacyclic triterpenes could tightly bind to the viral envelope HA protein, thus blocking the virus entry into host cells.
Lupane triterpenes and derivatives with antiviral activity
Baltina,Flekhter,Nigmatullina,Boreko,Pavlova,Nikolaeva,Savinova,Tolstikov
, p. 3549 - 3552 (2003)
Betulin and betulinic acid have been modified at the C-3 and C-28 positions and the antiviral activity of derivatives has been evaluated in vitro. It was found that simple modifications of the parent structure of lupane triterpenes produced highly effective agents against influenza A and herpes simplex type 1 viruses.
Biotransformation of betulinic and betulonic acids by fungi
Bastos, Denise Z.L.,Pimentel, Ida C.,de Jesus, Daniel A.,de Oliveira, Bras H.
, p. 834 - 839 (2007)
Betulinic acid (1), a triterpenoid found in many plant species, has attracted attention due to its important pharmacological properties, such as anti-cancer and anti-HIV activities. The closely related, betulonic acid (2) also has similar properties. In order to obtain derivatives potentially useful for detailed pharmacological studies, both compounds were submitted to incubations with selected microorganisms. In this work, both were individually metabolized by the fungi Arthrobotrys, Chaetophoma and Dematium, isolated from the bark of Platanus orientalis as well as with Colletotrichum, obtained from corn leaves; such fungal transformations are quite rare in the scientific literature. Biotransformations with Arthrobotrys converted betulonic acid (2) into 3-oxo-7β-hydroxylup-20(29)-en-28-oic acid (3), 3-oxo-7β,15α-dihydroxylup-20(29)-en-28-oic acid (4) and 3-oxo-7β,30-dihydroxylup-20(29)-en-28-oic acid (5); Colletotrichum converted betulinic acid (1) into 3-oxo-15α-hydroxylup-20(29)-en-28-oic (6) acid whereas betulonic acid (2) was converted into the same product and 3-oxo-7β,15α-dihydroxylup-20(29)-en-28-oic acid (4); Chaetophoma converted betulonic acid (2) into 3-oxo-25-hydroxylup-20(29)-en-28-oic acid (7) and both Chaetophoma and Dematium converted betulinic acid (1) into betulonic acid (2). Those fungi, therefore, are useful for mild, selective oxidations of lupane substrates at positions C-3, C-7, C-15, C-25 and C-30.
