27975-19-5

Usage

Uses

Used in Pharmaceutical Industry:
Isosteviol is used as a therapeutic agent for managing high blood pressure due to its antihypertensive activity. It helps in regulating blood pressure, providing relief to individuals suffering from hypertension.
Used in Diabetes Management:
Isosteviol is used as a glucose-lowering agent for individuals with diabetes. Its ability to reduce blood glucose levels makes it a potential candidate for the development of treatments and management strategies for diabetes.
Used in Anticancer Applications:
Isosteviol is used as an anticancer agent, particularly for its potential to suppress the growth and proliferation of cancer cells. It may be employed in the development of novel cancer treatments and therapies, targeting various types of cancer.
Used in Drug Delivery Systems:
To enhance the efficacy and bioavailability of Isosteviol, it can be incorporated into various drug delivery systems. These systems may include organic and metallic nanoparticles, which serve as carriers for Isosteviol, improving its delivery and therapeutic outcomes in different medical applications.

InChI:InChI=1/C20H30O3/c1-17-9-5-14-18(2)7-4-8-19(3,16(22)23)13(18)6-10-20(14,12-17)11-15(17)21/h13-14H,4-12H2,1-3H3,(H,22,23)

Upstream product

• 57817-89-7 stevioside 
• 29584-19-8 steviol 
• 57817-89-7 stevioside 
• 57817-89-7 stevioside 
• 50-99-7 D-glucose 
• 7664-93-9 sulfuric acid 
• 23963-60-2 (1R,4S,5R,9S,10R,13S)-5,9,13-trimethyl-15-oxo-14-oxatetracyclo[11.3.1.0^1,10.0^4,9]heptadecane-5-carboxylic acid 
• 1347574-22-4 13-methyl-16-oxo-17-nor-ent-kauran-19-oic acid-β-D-glucopyranosyl ester 
• 58543-16-1 rebaudioside A 

Downstream Products

• 1266676-06-5 16-oxo-beyerane-19-acid benzyl ester 
• 1163711-71-4 (4α,8β,13β)-13-methyl-16-oxo-17-norkauran-18-oic acid 4'-nitrobenzoyloxymethyl ester 
• 1428535-22-1 (3S,6aS,8aS,9R,12aS,12bS)-methyl 5-benzyl-3,9,12a-trimethyl-4-oxotetradecahydro-1H-3,6amethanonaphtho[2,1-c]azocine-9-carboxylate 
• 1428535-20-9 (3S,6aR,8aS,9R,12aS,12bR)-methyl 4-benzyl-3,9,12a-trimethyl-5-oxotetradecahydro-1H-3,6a-methanonaphtho[2,1-d]azocine-9-carboxylate 
• 1428535-27-6 C₂₈H₃₉NO₂ 
• 672948-33-3 (4R,4aS,6aR,9S,11aR,11bS,E)-methyl 8-(benzylimino)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate 
• 1448582-84-0 C₂₉H₃₇ClN₂O₂ 
• 1448582-85-1 C₂₉H₃₇ClN₂O₂ 
• 1448582-86-2 C₂₉H₃₇BrN₂O₂ 
• 1448582-87-3 C₂₉H₃₇BrN₂O₂ 
• 1448582-88-4 C₂₉H₃₇BrN₂O₂ 
• 1448582-89-5 C₃₀H₄₀N₂O₂ 
• 1448582-90-8 C₃₀H₄₀N₂O₂ 
• 1448582-91-9 C₃₀H₄₀N₂O₂ 

Relevant academic research and scientific papers

Reaction coupling separation for isosteviol production from stevioside catalyzed by acidic ion-exchange resin

Abstract: Isosteviol, a prodrug used to be obtained via Wagner–Meerwein rearrangement from steviol with low yield and long reaction?time. Herein, an in-situ separation-coupling-reaction is presented to prepare isosteviol from the natural sweetener stevioside. Simply with in-situ water-washing, the product containing 92.98% purity of isosteviol was obtained with a stevioside conversion of 97.23% from a packet bed reactor without further separation. Within the assayed inorganic acid, organic acids and acidic ionic liquids, the acidic ion-exchange resins provided higher product specificity towards isosteviol. Furthermore, comparing to 5-Fluorouracil, the product presented similar and even stronger inhibition on proliferation of the assayed human cancer cells in a time and dose-dependence by causing cell phase arrest. Isosteviol treatment caused G1 arrest on SGC-7901, HCT-8 and HCT-116 cells, S arrest on HepG2, Huh-7 and HepG3B cells, and G2 arrest on MGC-803 cells, respectively. Graphic abstract: Reaction coupling separation for isosteviol production catalyzed by acidic ion-exchange resin.[Figure not available: see fulltext.]

(-)-isosteviol as a versatile ex-chiral-pool building block for organic chemistry

(-)-Isosteviol is readily available in large quantities by the acidic treatment of a common alternative sweetener. The two functional groups of (-)-isosteviol are presented on the same side of the ent-beyerane scaffold with a mutual C-C distance of about

Synthesis, Structure, and Cytotoxic Activities of a Novel Lactam of the Diterpenoid Isosteviol

A novel compound lactam of 15β-hydroxymethylisosteviol ethyl ester 3 has been synthesized and structurally characterized by IR, NMR, and HR-MS. Its X-ray crystallographic analysis revealed that the nitrogen is attached to C-13 instead of C-15. The reaction mechanism was discussed, and the title compound was further evaluated against HCT-116, HGC-27, and JEKO-1 cells by the MTT assay. The results demonstrated that compound 3 exhibited better cytotoxic activities than its corresponding precursor isosteviol.

Structural analysis of isosteviol and related compounds as DNA polymerase and DNA topoisomerase inhibitors

Isosteviol (ent-16-ketobeyeran-19-oic acid) is a hydrolysis product of stevioside, which is a natural sweetener produced in the leaves of Stevia rebaudiana (Bertoni) Bertoni. In this report, we prepared isosteviol and related compounds from stevioside by microbial transformation and chemical conversion and assayed the inhibitory activities toward DNA metabolic enzymes and human cancer cell growth. Among twelve compounds obtained, only isosteviol (compound 3) potently inhibited both mammalian DNA polymerases (pols) and human DNA topoisomerase II (topo II), and IC50 value for pol α was 64.0 μM. This compound had no inhibitory effect on higher plant (cauliflower) pols, prokaryotic pols, human topo I, and DNA metabolic enzymes such as human telomerase, T7 RNA polymerase, and bovine deoxyribonuclease I. With pol α, isosteviol acted non-competitively with the DNA template-primer and nucleotide substrate. Isosteviol prevented the growth of human cancer cells, with LD 50 values of 84-167 μM, and 500 μg of the compound caused a marked reduction in TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation (inhibitory effect, 53.0%). The relationship between the structure of stevioside-based compounds and these activities were discussed.

Synthesis and anti-hepatitis B virus activity of C4 amide-substituted isosteviol derivatives

A series of novel isosteviol derivatives having C4-amide substituents were synthesized in order to test for antiviral effects against the hepatitis B virus (HBV) in vitro. Among them, IN-4 [N-(propylcarbonyl)-4α-amino-19-nor-ent-16-ketobeyeran] (5) exhibited inhibitory activity against secretion of HBsAg and HBeAg as well as inhibition of HBV DNA replication. Therefore, the mechanism of its antiviral activity was further analyzed using HBV-transfected Huh7 cells. Exposure to IN-4 produced minimal inhibitory effects on viral precore/pregenomic RNA expression. However, expression levels of the 2.4/2.1-kb preS/major S RNA of the viral surface gene significantly decreased, along with intracellular levels of HBV DNA. A promoter activity analysis demonstrated that IN-4 significantly inhibited viral X, S, and preS expression levels but not viral core promoter activities. In particular, IN-4 was observed to significantly inhibit HBV gene regulation by disrupting nuclear factor (NF)-κB-associated promoter activity. In addition, the nuclear expression of p65/p50 NF-κB member proteins was attenuated following IN-4 treatment, while cytoplasmic IκBα protein levels were enhanced. Meanwhile, IN-4 was observed to inhibit the binding activity of NF-κB to putative DNA elements. Furthermore, transfection of a p65 expression plasmid into Huh7 cells significantly reversed the inhibitory effect of IN-4 on HBV DNA levels, providing further evidence of the central role of NF-κB in its antiviral mechanism. It is therefore suggested that IN-4 inhibits HBV by interfering with the NF-κB signaling pathway, resulting in downregulation of viral gene expression and DNA replication.

Endothelium-independent vasorelaxation effects of 16-O-acetyldihydroisosteviol on isolated rat thoracic aorta

Aims: The aim of this study is to investigate the vasorelaxant effect of 16-O-acetyldihydroisosteviol (ADIS) and its underlying mechanisms in isolated rat aorta. Main methods: Rat aortic rings were isolated, suspended in organ baths containing Kreb's solution, maintained at 37°C, and mounted on tungsten wire and continuously bubbled with a mixture of 95% O2 and 5% CO2 under a resting tension of 1 g. The vasorelaxant effects of ADIS were investigated by means of isometric tension recording experiment. Key findings: ADIS (0.1 μM-3 mM) induced relaxation of aortic rings pre-contracted by phenylephrine (PE, 10 μM) and KCl (80 mM) with intact-endothelium (Emax = 79.26 ± 3.74 and 79.88 ± 3.79, respectively) or denuded-endothelium (Emax = 88.05 ± 3.69 and 78.22 ± 6.86, respectively). In depolarization Ca2+-free solution, ADIS inhibits calcium chloride (CaCl2)-induced contraction in endothelium-denuded rings in a concentration-dependent manner. In addition, ADIS attenuates transient contractions in Ca2+-free medium containing EGTA (1 mM) induced by PE (10 μM) and caffeine (20 mM). By contrast, relaxation was not affected by tetraethylammonium (TEA, 5 mM), 4-aminopyridine (4-AP, 1 mM), glibenclamide (10 μM), barium chloride (BaCl2, 1 mM), and 1H-[1,2,3]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, 1 μM). Significance: These findings reveal the vasorelaxant effect of ADIS, through endothelium-independent pathway. It acts as a Ca2 + channel blocker through both intracellular and extracellular Ca2 + release.

Discovery of lysosome-targeted covalent anticancer agents based on isosteviol skeleton

Covalent drugs play corresponding bioactivities by forming covalent bonds with the target, which possess many significant pharmacological advantages including high potency, ligand efficiency, and long-lasting effects. However, development of covalent inhibitors is a challenge due to their presumed indiscriminate reactivity. Here, we report the discovery of series of lysosome-targeting covalent anticancer agents by introducing nitrogenous bases to the modified isosteviol skeleton in order to minimize the toxicity and increase the selectivity. By introducing the electrophilic α, β-unsaturated ketones into the A- and D-rings of isosteviol, the cytotoxicity of the obtained compounds were greatly increased. Further nitrogen-containing modifications to the D-ring led to the discovery of novel molecules that targeted lysosomes, and of which, compound 30 was the most potent and selective antiproliferative one to kill A549 cells in vitro and in vivo. Mechanism investigation revealed that compound 30 was trapped into lysosomes and damaged lysosomes to cause cell death.

The neuroprotective effects of isosteviol against focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats

Occlusion of a cerebral artery impairs blood flow leading to neuronal death. Reperfusion of the tissue is associated with inflammation, increased reactive oxygen species, necrosis and apoptosis. Hence, damage to the brain will continue even after the blood flow is restored. Isosteviol has been demonstrated to have protective effects against ischemia-reperfusion (IR) injury in the rat heart and the current study was undertaken to determine whether it is also effective in preventing IR injury in the brain. Rats were divided into six groups: a sham-operation control group and 5 IR groups that were pre-treated with either isosteviol 5 mg-kg-1,10 mg-kg-1,20 mg-kg -1, nimodipine 5 mg-kg-1, or saline. Cerebral ischemia was in-duced for 2 hours. Twenty-two hours after reperfusion the rats were assessed for neurobeha-vioral deficit, infarct volume, histological changes, and malondialdehyde, superoxide dismutase (SOD), Bcl-2 and NF-kB levels in brain tissue. Pre-treatment with isosteviol reduced infarct volume, ameliorated cell death and infiltration of neutrocytes, improved neuro-locomotor activity, increased SOD activity, induced Bcl-2, suppressed lipid superoxidation and the expression of NF-kB, and therefore retarded necrosis and apoptosis of neurons and inflammation. These positive effects were dose-dependent with an isosteviol dose of 20 mg-kg-1, thus being as effective as nimodipine.

Microbial Transformation of Isosteviol and Inhibitory Effects on Epstein-Barr Virus Activation of the Transformation Products

Microbial transformation of isosteviol (2), a beyerane-type diterpenoid obtained from stevioside (1) by acid hydrolysis, yielded 7β -hydroxyisosteviol (3), 11β-hydroxyisosteviol (5), and 12β -hydroxyisosteviol (6) by the fungus Aspergillus niger, 17-hydroxyisosteviol (7) by the fungus Glomerella cingulata, and 3 and 7-oxoisosteviol (4) by the fungus Mortierella elongate. The five metabolites, 3-7, along with 1 and 2 were evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the diterpenes tested showed potent inhibitory effects, with the five metabolites 3-7 exhibiting more potent effects.

Potent vasorelaxant analogs from chemical modification and biotransformation of isosteviol

Isosteviol (1) has been reported to exhibit moderate vasorelaxant activity. In order to enhance the bioactivity of this compound, chemical modification of 1 to the dihydro analog, ent-16β-hydroxybeyeran-19-oic acid (2), was undertaken. Compound 2 was then converted to the corresponding acetate derivative, ent-16β-acetoxybeyeran-19-oic acid (3). Biotransformation of compounds 1-3 by the fungus Cunninghamella echinulata NRRL 1386 was investigated and the metabolites 4-9 were obtained. The substrates and their metabolites were subjected to in vitro rat aorta relaxant activity evaluation. The metabolite 4, ent-7α-hydroxy-16-ketobeyeran-19-oic acid, exhibited the most highly potent activity, with EC50 of 3.46 nM, whereas the parent compound 1 showed relatively low activity (EC50 57.41 nM). A 17-fold increase in vasorelaxant activity of the analog 4 relative to compound 1 is of particular significant. Compound 4 exerted vasorelaxant activity at particularly low concentration and the vasorelaxant profile reached maximum at relatively low concentration, especially when compared with acetylcholine, the positive control.