1061-54-7Relevant articles and documents
Hardman,Sofowora
, p. 645,648 (1970)
Application of hypoiodite-mediated aminyl radical cyclization to synthesis of solasodine acetate
Kou, Yi,Koag, Myong Chul,Cheun, Young,Shin, Aram,Lee, Seongmin
, p. 1069 - 1074 (2012)
Solasodine acetate, an anticancer steroidal alkaloid, was synthesized from diosgenin in 8 steps with an overall yield of 23%. A key synthetic step involves the formation of 5/6-oxazaspiroketal moiety via hypoiodite-mediated aminyl radical cyclization of a steroidal primary amine.
An improved synthesis of pennogenin
Gao, Ran,Shi, Yong,Tian, Wei-Sheng
, p. 1717 - 1721 (2019)
An improved synthesis of pennogenin, a bioactive component of Chinese herb “Chonglou” (Paris), is described. A ring-switching process opened the ring E of diosgenin and allowed the use of a hydroxyl-directed diboration/oxidation to introduce C17α-OH, hence eliminating the use of OsO4. This strategy might be rendered to synthesize similar steroids with C17α-OH.
In vitro neuroprotective and anti-inflammatory activities of natural and semi-synthetic spirosteroid analogues
García-Pupo, Laura,Zaldo-Castro, Armando,Exarchou, Vassiliki,Tacoronte-Morales, Juan Enrique,Pieters, Luc,Berghe, Wim Vanden,Nu?ez-Figueredo, Yanier,Delgado-Hernández, René
, (2016)
Two spirosteroid analogues were synthesized and evaluated for their in vitro neuroprotective activities in PC12 cells, against glutamate-induced excitotoxicity and mitochondrial damage in glucose deprivation conditions, as well as their anti-inflammatory potential in LPS/IFNγ-stimulated microglia primary cultures. We also evaluated the in vitro anti-excitotoxic and anti-inflammatory activities of natural and endogenous steroids. Our results show that the plant-derived steroid solasodine decreased PC12 glutamate-induced excitotoxicity, but not the cell death induced by mitochondrial damage and glucose deprivation. Among the two synthetic spirosteroid analogues, only the (25R)-5α-spirostan-3,6-one (S15) protected PC12 against ischemia-related in vitro models and inhibited NO production, as well as the release of IL-1β by stimulated primary microglia. These findings provide further insights into the role of specific modifications of the A and B rings of sapogenins for their neuroprotective potential.
Novel diosgenin derivatives containing 1,3,4-oxadiazole/thiadiazole moieties as potential antitumor agents: Design, synthesis and cytotoxic evaluation
Zhang, Jinling,Wang, Xuemei,Yang, Jifang,Guo, Lina,Wang, Xiaoli,Song, Bo,Dong, Wei,Wang, Wenbao
, (2020)
Diosgenin, a naturally occurring steroidal saponin, has been confirmed to possess potent anticancer properties. In the current work, two series of novel diosgenin derivatives bearing 1,3,4-oxadiazole (6a?6e and 7a?7e) or 1,3,4-thiadiazole (8a?8e and 9a?9e) moieties were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, A549, MCF-7 and HCT-116) and normal human gastric epithelial cells (GES-1) using the MTT assay in vitro. The results showed that compounds 8d and 9d exhibited significant cytotoxic activities against the HepG2 and A549 cells, being more potent than their parent compound diosgenin. Furthermore, the 1,3,4-thiadiazole series of compounds generally exhibited stronger cytotoxicity compared with the 1,3,4-oxadiazole series against HepG2 and A549 cells, and the substitution of 3-pyridyl group at the C5 position of the 1,3,4-thiadiazole ring was the preferred option for these compounds to display significant cytotoxic activities. Compound 8d showed potent cytotoxic activity against A549 cell line (IC50 = 3.93 μM) and was 6.7-fold more potent than diosgenin (IC50 = 26.41 μM). Moreover, compound 8d displayed low toxicity against GES-1 cells (IC50 = 420.4 μM), showing specificity between normal and tumor cells. Further cellular mechanism studies in A549 cells indicated that compound 8d triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential, which was associated with up-regulation of Bax, down-regulation of Bcl-2 and activation levels of the caspase cascade. The above results indicated that compound 8d may be used as a promising skeleton for antitumor agents with improved efficacy.
Design, Synthesis and Biological Evaluation of Steroidal Glycoconjugates as Potential Antiproliferative Agents
Du, Zhichao,Li, Guolong,Ge, Haixia,Zhou, Xiaoyang,Zhang, Jian
, p. 1488 - 1498 (2021)
To systematically evaluate the impact of neoglycosylation upon the anticancer activities and selectivity of steroids, four series of neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized according to the neoglycosylation approach. The structures of all the products were elucidated by NMR analysis, and the stereochemistry of C20-MeON-pregnenolone was confirmed by crystal X-ray diffraction. The compounds′ cytotoxicity on five human cancer cell lines was evaluated using a Cell Counting Kit-8 assay, and structure–activity relationships (SAR) are discussed. 2-deoxy-d-glucoside 5 k displayed the most potent antiproliferative activities against HepG2 cells with an IC50 value of 1.5 μM. Further pharmacological experiments on compound 5 k on HepG2 cells revealed that it could cause morphological changes and cell-cycle arrest at the G0/G1 phase and then induced the apoptosis, which might be associated with the enhanced expression of high-mobility group Box 1 (HMGB1). Taken together, these findings prove that the neoglycosylation of steroids could be a promising strategy for the discovery of potential antiproliferative agents.
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Sato,Lathan
, p. 6067 (1953)
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Continuous Flow Synthesis of 16-Dehydropregnenolone Acetate, a Key Synthon for Natural Steroids and Drugs
Mancino, Valentina,Cerra, Bruno,Piccinno, Alessandro,Gioiello, Antimo
, p. 600 - 607 (2018)
A telescoped multistep process to provide the continuous delivery of 16-dehydropregnenolone acetate (16-DPA) from diosgenin is described. The method was evaluated through batch screenings that helped to identify critical bottlenecks and flowability, and the best conditions were optimized in flow systems before the individual steps were telescoped together into a single integrated flow process. Further highlights of our approach include the use of efficient in-line extraction operations and reaction monitoring, the avoidance of time-consuming purifications between steps, and improvement of efficiency and safety standards.
Supramolecular prodrug micelles based on the complementary multiple hydrogen bonds as drug delivery platform for thrombosis therapy
Li, Wen'En,Wang, Haibo,Wei, Zeliang,Ning, Juewei,Ma, Limei,Zheng, Huajie,Niu, Hai,Huang, Wen
, p. 62478 - 62484 (2016)
To improve the effect of thrombosis therapy, an amphiphilic supramolecular prodrug consisting of diosgenin derivative (theophylline-diosgenin) and uracil-terminated poly(ethylene glycol) (PEG-U) was designed and synthesized successfully. The prodrug could self-assemble into micelles which was not only enhanced the drug solubility but also prolonged systemic circulation. Bleeding time assay confirmed that the micelles have a better antithrombotic activity compared to diosgenin in vivo, and platelet aggregation assay in vitro got the same results. The low cytotoxicity of supramolecular copolymer micelles was confirmed by MTT assay against LO2/HK-2 cells and acute toxicity studies in mice. Based on these results, the supramolecular prodrug micelles are very promising candidates for thrombosis therapy.
First synthesis of furostans bearing a 1, 3-dioxane ring at C-26. XRD, Hirshfeld surfaces analysis, DFT studies
Prakash, Rohit,Sethi, Arun,Singh, Praveer,Singh, Ranvijay Pratap,Yadav, Priyanka
, (2021/09/07)
The regioselective opening of ring F in diosgenin derivatives, in the presence of 2-substituted 1,3-propanediol, yielded new furostans bearing a 1,3-dioxane ring at C-26. The structures of these synthesized compounds 1e, 2a, 2b, 2c, 2d and 2e were established on the basis of spectroscopic data, including 1D and 2D NMR and ESI-HRMS. Single crystal X-ray diffraction analysis of 2e (22R,25R)-26-(5?bromo-5-nitro-1,3-dioxanyl)furost-5-en-3-yl acetate not only helped in structural identification but also helped in ascertaining its stereochemistry. The molecular geometry of these compounds was calculated in ground state by density functional theory (DFT/B3LYP) using 6–31 G (d, p) basis set. The electronic properties such as HOMO and LUMO energy were calculated by using time dependent density functional theory (TD-DFT). The topological parameters-electron density (ρBCP), Laplacian of electron density (?2ρ(rBCP)), energy parameters-kinetic electron energy density (GBCP), potential electron density (VBCP) and the total electron energy density (HBCP) at the bond critical points (BCP) were analyzed by ‘Atoms in molecules’ AIM theory. The Hirshfeld surface analysis helped in identifying important intermolecular interactions in 2e. Global reactivity descriptors and molecular electrostatic potential for compounds have also been determined. First hyperpolarizability (β0) of compounds has been computed to evaluate non-linear optical (NLO) response.
DG-8d, a novel diosgenin derivative, decreases the proliferation and induces the apoptosis of A549 cells by inhibiting the PI3k/Akt signaling pathway
Chen, Xiaoting,Chen, Zhe,Fan, Li,Jia, Yongming,Ma, Liwei,Ni, Shiyu,Wang, Wenbao
, (2021/08/09)
Lung neoplasm has a relatively poor prognosis, and the clinical efficacy of targeted medicine remains unsatisfactory. Therefore, the development of novel efficient anti-lung cancer drugs is urgently needed. In our previous study, we showed that a novel diosgenin derivative 8d (DG-8d), which contained 5-(3-pyridyl)-1,3,4-thiadiazole moiety, had significant cytotoxic activity on human tumor cells, especially the A549 cells. However, the underlying mechanism of DG-8d was unknown. In this study, the pharmacological effect of DG-8d on the A549 cells was inspected. Method: Cell viability and apoptosis were detected by CCK-8 assays, morphological changes and quantitative analysis of flow cytometry. Levels of gene and protein expression of apoptosis-related and PI3k/Akt pathway were evaluated by qRT-PCR, immunostaining and Western blot analysis. Result: The findings proved that DG-8d could inhibit cell growth and induce apoptosis. The effect of DG-8d on the proliferation and apoptosis in the A549 cells were improved with LY294002 (PI3K inhibitor). Moreover, the effect of DG-8d on apoptosis was further confirmed by AO-EB dye, mitochondrial depolarization and accrued intracellular ROS. Gene and protein detection showed that DG-8d or DG-8d combined with LY294002 could down-regulate signaling molecules of Bcl-2, PI3k, p-Akt, p-FoxO3a and up-regulate signaling molecules of Bax snd Bim. In addition, nuclear translocation of FoxO3a was observed significantly in the cells. Conclusion: DG-8d could inhibit the proliferation and induce the apoptosis of the A549 cells, which maybe mainly because of the suppression of the PI3k/Akt pathways. Finally, we believe that DG-8d can be developed as a possible agent for carcinoma therapy.
