Carbamate derivatives of betulinic acid and betulin with selective cytotoxic activity

Kommera, Harish; Kaluđerović, Goran N.; Dittrich, Sebastian; Kalbitz, Jutta; Dräger, Birgit; Mueller, Thomas; Paschke, Ralf

doi:10.1016/j.bmcl.2010.04.004

Cited by 55 publications

(36 citation statements)

References 22 publications

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“…Among the tested compounds, 3 and 6-9 showed moderate cytotoxicity against all tumor cells, while compound 8 exhibited the most potent cytotoxicity with IC 50 value of 7.26-12.37 μM. Triterpenoid derivatives have been one of the most interesting areas of research in the past few years due to their broad range of biological and medicinal properties [18][19][20]. Davinvolunic acid A (1), euscaphic acid (4), and myrianthic acid (5), with an α-oriented hydroxyl group at C-3, were found to show no cytotoxicity against all the three tumor cell lines tested at 100 μM.…”

Section: Resultsmentioning

confidence: 99%

Three New Ring-A Modified Ursane Triterpenes from Davidia involucrata

2014

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Three new ursane triterpenes, 3α,19α-dihydroxy-2-nor-urs-12-en-23,28-dioic acid-23-methyl ester (1), 19α3-dihydroxy-3-oxo-2-nor-urs-12-en-28-oic acid (2), and 2,3-seco-3-methoxy-3,19α3-trihydroxy-urs-12-en-2-al-28-oic acid (3), were isolated from the MeOH extract of the branch barks of Davidia involucrata, together with six known compounds. Their structures were elucidated by means of various spectroscopic analyses. The isolated triterpenes provide important evolutionary and chemotaxonomic knowledge about the monotypic genus Davidia. Five of the identified compounds showed moderate cytotoxicities against the cell proliferation of SGC-7901, MCF-7, and BEL-7404 with IC 50 range from 7.26 to 47.41 μM.

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Section: Resultsmentioning

confidence: 99%

Three New Ring-A Modified Ursane Triterpenes from Davidia involucrata

2014

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“…Similarly, the possibility of chemically modifying the BA to make it able to cross the BBB seems very attractive, as it has been shown to be effective for other triterpenoids, eg oleanolic acid in EAE [35] . As a matter of fact, the strategy of chemical modification has already been applied to betulinic acid, as its derivatives have been investigated for their anti-cancer properties [36,37] . Finally, besides demonstrating the potential therapeutic effects in neuroinflammation, our results also contribute to the understanding of BA anti-cancer properties.…”

Section: Wwwchinapharcom Blaževski J Et Almentioning

confidence: 99%

Betulinic acid regulates generation of neuroinflammatory mediators responsible for tissue destruction in multiple sclerosis in vitro

et al. 2013

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Aim: To investigate the influences of betulinic acid (BA), a triterpenoid isolated from birch bark, on neuroinflammatory mediators involved in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis in vitro. Methods: Encephalitogenic T cells were prepared from draining lymph nodes and spinal cords of Dark Agouti rats 8 to 10 d after immunization with myelin basic protein (MBP) and complete Freund's adjuvant. Macrophages were isolated from the peritoneal cavity of adult untreated rats. Astrocytes were isolated from neonatal rat brains. The cells were cultured and then treated with different agents. IFN-γ, IL-17, iNOS and CXCL12 mRNA levels in the cells were analyzed with RT-PCR. iNOS and CXCL12 protein levels were detected using immunoblot. NO and ROS generation was measured using Griess reaction and flow cytometry, respectively. Results: In encephalitogenic T cells stimulated with MBP (10 μg/mL), addition of BA inhibited IL-17 and IFN-γ production in a dosedependent manner. The estimated IC 50 values for IL-17 and IFN γ were 11.2 and 63.8 μmol/L, respectively. When the macrophages were stimulated with LPS (10 ng/mL), addition of BA (50 μmol/L) significantly increased ROS generation, and suppressed NO generation. The astrocytes were stimulated with ConASn containing numerous inflammatory mediators, which mimicked the inflammatory milieu within CNS; addition of BA (50 μmol/L) significantly increased ROS generation, and blocked ConASn-induced increases in iNOS and CXCL12 mRNA levels, but did not affect iNOS and CXCL12 protein levels. Importantly, in both the macrophages and astrocytes, addition of BA (50 μmol/L) inhibited lipid peroxidation.

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“…In contrast, the 3-amino analogue 79 obtained by reductive ammination of betulonic acid (5) showed anti-MEL-2 activity comparable with betulinic acid (1) (Kim et al, 1998). The nitrogenous derivatives of betulinic acid (1) in position 3 can also include carbamoyl derivatives 82 -84 synthesized according to the literature (Kommera et al, 2010). While the 3-phenylcarbamoyl derivative of betulinic acid -83 -was active against 518A2, 3-ethyl carbamates 82, 84 showed activity comparable to or better than betulinic acid (1).…”

Section: Derivatization Of Betulinic Acid (1) and Betulin (3) In Posimentioning

confidence: 99%