1061-54-7Relevant academic research and scientific papers
Photoinduced isomerization of 23-oxosapogenins: Conformational analysis and spectroscopic characterization of 22-isosapogenins
Jastrzeì?bska, Izabella,Górecki, Marcin,Frelek, Jadwiga,Santillan, Rosa,Siergiejczyk, Leszek,Morzycki, Jacek W.
, p. 11257 - 11269 (2012)
The first synthesis of 22-isospirostane derivatives is described. They were obtained by photochemical isomerization of 23-oxosapogenins. The structure of 23-oxo-22-isotigogenin acetate (12) was proved by a single crystal X-ray diffraction, while structures of 23-oxo-22-isodiosgenin acetate (13) and 23-oxo-22-isosarsasapogenin acetate (14) were elucidated by spectroscopic methods. 22-Isodiosgenin acetate (17) was obtained by NaBH4 reduction of the 23-oxo derivative 13 followed by the two-step Barton-McCombie deoxygenation procedure. Conformational analysis of 22-iso compounds was carried out with CD and NMR, as well as DFT calculations.
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.
Synthesis and anti-glioma activity of 25(R)-spirostan-3β,5α,6β,19-tetrol
Leng, TianDong,Zhang, JingXia,Xie, Jun,Zhou, ShuJia,Huang, YiJun,Zhou, YueHan,Zhu, WenBo,Yan, GuangMei
, p. 224 - 229 (2010)
Malignant gliomas are common and aggressive brain tumours in adults. The rapid proliferation and diffuse brain migration are the main obstacles to successful treatment. Here, we show 25(R)-spirostan-3β,5α,6β,19-tetrol, a polyhydroxy steroid, is capable of suppressing proliferation and migration of C6 malignant glioma cells in a concentration-dependent manner. The compound 25(R)-spirostan-3β,5α,6β,19-tetrol was synthesised by seven steps starting from diosgenin in 8.55% overall yield. The structures of the synthetic compounds were characterised by infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR spectra and EA.
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.
Bivalent furostene carbamates as antiproliferative and antiinflammatory agents
Pathak, Nandini,Fatima, Kaneez,Singh, Sneha,Mishra, Divya,Gupta, Amit Chand,Kumar, Yogesh,Chanda, Debabrata,Bawankule,Shanker, Karuna,Khan, Feroz,Gupta, Atul,Luqman, Suaib,Negi, Arvind S.
, (2019)
Breast cancer is the most prevalent cancer in women affecting about 12% of world's female population. It is a multifactorial disease, mostly invasive in nature. Diosgenin and related compounds are potent antiproliferative agents. Carbamate derivatives have been synthesized at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin. Compound 10 possessed significant antiproliferative activity against human breast cancer cells by arresting the population at G1 phase of cell division cycle and induced apoptosis. Induction of apoptosis was observed through the caspase signalling cascade by activating caspase-3. Moreover, carbamate 10 exhibited moderate antiinflammatory activity by decreasing the expression of cytokines, TNF-α and IL-6 in LPS-induced inflammation in primary macrophage cells. Furthermore, compound 10 significantly reduced Ehrlich ascites carcinoma significantly in mice. It was well tolerated and safe in acute oral toxicity in Swiss albino mice. The concomitant anticancer and antiinflammatory properties of carbamate 10 are important and thus, can further be optimized for a better anti-breast cancer candidate.
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.
Synthesis and anti–tumour, immunomodulating activity of diosgenin and tigogenin conjugates
Michalak,Krzeczyński,Cie?lak,Cmoch,Cybulski,Królewska-Golińska,Ka?mierczak-Barańska,Trzaskowski,Ostrowska
, (2020)
A series of novel diosgenin (DSG) and tigogenin (TGG) derivatives with diosgenin or tigogenin steroid aglycons linked to levulinic and 3,4–dihydroxycinnamic acids, dipeptides and various amino acids by an ester bond at the C3–oxygen atom of the steroid skeleton has been synthesized. Diosgenyl esters have been prepared by an esterification reaction (DCC/DMAP) of diosgenin with the corresponding acids. All analogues have been evaluated in vitro for their antiproliferative profile against cancer cell lines (MCF–7, MDA–MB–231, PC–3) and human umbilical vein endothelial cells (HUVEC). Analogue2c (l–serine derivative of TGG), the best representative of the series showed IC50 of 1.5 μM (MCF–7), and induced apoptosis in MCF–7 by activating caspase–3/7. The immunomodulatory properties of six synthesized analogues have been determined by examining their effects on the expression of cytokine genes essential for the functioning of the human immune system (IL–1, IL–4, IL–10, IL–12 and TNF–α). Biological evaluation has revealed that new compounds 4c and 16a do not induce the expression of pro–inflammatory cytokines in THP–1 cells after the lipopolysaccharide (LPS) stimulation. They also stimulate the expression of anti–inflammatory IL–10 that acts stronger than diosgenin itself. An in silico ADME properties(absorption, distribution, metabolism, excretion) study was also performed to predict the pharmacokinetic profile of the synthesized compounds. To shed light on the molecular interactions between the synthesized compounds and the glucocorticoid receptor and the estrogen receptor, 2c, 4c and 16a compounds were docked into the active binding sites of these receptors. The in silico and in vitro data suggested that this new group of compounds might be considered as a promising scaffold for further modification of more potent and selective anticancer and immunomodulatory agents.
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.
(22β,25R)-3β-Hydroxy-spirost-5-en-7-iminoxy-heptanoic acid exhibits anti-prostate cancer activity through caspase pathway
Hamid,Kaushal, Tanu,Ashraf, Raghib,Singh, Arjun,Chand Gupta, Amit,Prakash, Om,Sarkar, Jayanta,Chanda, Debabrata,Bawankule,Khan, Feroz,Shanker, Karuna,Aiyelaagbe,Negi, Arvind S.
, p. 43 - 52 (2017)
Prostate cancer is one of the most common cancers in men. Diosgenin and related compounds are potential cytotoxic agents. Twelve diverse analogues of long chain fatty acid/ester of diosgenin-7-ketoxime have been prepared. Six of the analogues exhibited significant anticancer activity against a panel of human cancer cell lines with IC50ranging from 12 to 35?μM. Compound 16, the best representative of the series exerted S phase arrest in DU145 prostate cancer cells and induced apoptosis through caspase pathway. Additionally, these analogues inhibited lipopolysaccharide induced pro-inflammatory cytokines (TNF-α and IL-6) up to 47.7% and 23.3% respectively. Compound 16 was found to be safe in acute oral toxicity in Swiss albino mice up to 300?mg/kg dose. The anticancer and antiinflammatory properties of compound 16 are important and can further be optimized for a better anti-prostate cancer candidate.
