Astragenol

Microbial Transformation of Cycloastragenol and Astragenol by Endophytic Fungi Isolated from Astragalus Species.[Pubmed:31713424]

J Nat Prod. 2019 Nov 22;82(11):2979-2985.

Biotransformation of Astragalus sapogenins (cycloAstragenol (1) and Astragenol (2)) by Astragalus species originated endophytic fungi resulted in the production of five new metabolites (3, 7, 10, 12, 14) together with 10 known compounds. The structures of the new compounds were established by NMR spectroscopic and HRMS analysis. Oxygenation, oxidation, epoxidation, dehydrogenation, and ring cleavage reactions were observed on the cycloartane (9,19-cyclolanostane) nucleus. The ability of the compounds to increase telomerase activity in neonatal cells was also evaluated. After prescreening studies to define potent telomerase activators, four compounds were selected for subsequent bioassays. These were performed using very low doses ranging from 0.1 to 30 nM compared to the control cells treated with DMSO. The positive control cycloAstragenol and 8 were found to be the most active compounds, with 5.2- (2 nM) and 5.1- (0.5 nM) fold activations versus DMSO, respectively. At the lowest dose of 0.1 nM, compounds 4 and 13 provided 3.5- and 3.8-fold activations, respectively, while cycloAstragenol showed a limited activation (1.5-fold).

Cycloartane-type sapogenol derivatives inhibit NFkappaB activation as chemopreventive strategy for inflammation-induced prostate carcinogenesis.[Pubmed:29678446]

Steroids. 2018 Jul;135:9-20.

Chronic inflammation is associated to 25% of cancer cases according to epidemiological data. Therefore, inhibition of inflammation-induced carcinogenesis can be an efficient therapeutic approach for cancer chemoprevention in drug development studies. It is also determined that anti-inflammatory drugs reduce cancer incidence. Cell culture-based in vitro screening methods are used as a fast and efficient method to investigate the biological activities of the biomolecules. In addition, saponins are molecules that are isolated from natural sources and are known to have potential for tumor inhibition. Studies on the preparation of analogues of cycloartane-type sapogenols (9,19-cyclolanostanes) have so far been limited. Therefore we have decided to direct our efforts toward the exploration of new anti-tumor agents prepared from cycloAstragenol and its production artifact Astragenol. The semi-synthetic derivatives were prepared mainly by oxidation, condensation, alkylation, acylation, and elimination reactions. After preliminary studies, five sapogenol analogues, two of which were new compounds (2 and 3), were selected and screened for their inhibitory activity on cell viability and NFkappaB signaling pathway activity in LNCaP prostate cancer cells. We found that the Astragenol derivatives 1 and 2 as well as cycloAstragenol derivatives 3, 4, and 5 exhibited strong inhibitory activity on NFkappaB signaling leading the repression of NFkappaB transcriptional activation and suppressed cell proliferation. The results suggested that these molecules might have significant potential for chemoprevention of prostate carcinogenesis induced by inflammatory NFkappaB signaling pathway.

Smith degradation, an efficient method for the preparation of cycloastragenol from astragaloside IV.[Pubmed:24613799]

Fitoterapia. 2014 Jun;95:42-50.

CycloAstragenol (CA) is the genuine sapogenin of astragaloside IV (ASI). This study focuses on the preparation of CA from ASI. Five hydrolysis methods were compared including H2SO4 hydrolysis, HCl hydrolysis, two-phase acid hydrolysis, mild acid hydrolysis, and Smith degradation. Seven hydrolysis products were purified, and five of them were identified as new compounds. The results indicated that Smith degradation was the most effective approach to prepare CA. In contrast, mild acid hydrolysis produced CA at a low yield, accompanied with the artificial sapogenin Astragenol. The other three acid hydrolysis methods mainly produced Astragenol. Furthermore, the reaction conditions for Smith degradation were optimized as follows: ASI was dissolved in 60% MeOH-H2O solution, oxidized with 5 equiv. NaIO4 for 12h, followed by reduction with 3 equiv. NaBH4 for 4h, and finally acidified with 1M H2SO4 at pH2 for 24h. Under the optimal conditions, CA could be prepared from ASI at a yield of 84.4%.