Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3β,12β,25-triol derivatives as α-glucosidase and PTP1B inhibitors.

ABSTRACT: The dammarane triterpenoid (20S,24R)-epoxy-dammarane-3β,12β,25-triol obtained from Cyclocarya paliurus in our previous study showed inhibitory activity on α-glucosidase in vitro with an inhibitory ratio of 32.2% at the concentration of 200 μM. In order to reveal the structure-activity relationships (SARs) and get more active compounds, 42 derivatives of (20S,24R)-epoxy-dammarane-3β,12β,25-triol were synthesized by chemical modification on the hydroxyls (C-3 and C-12), rings A and E, and assayed for their α-glucosidase and PTP1B inhibitory activities. Two compounds (8, 26) increased activity against α-glucosidase, and four compounds (8, 15, 26, 42) significantly inhibited PTP1B. It was noted that compounds 8 and 26 could inhibit both α-glucosidase and PTP1B as dual-target inhibitors with IC₅₀ values of 489.8, 467.7 μM (α-glucosidase) and 319.7, 269.1 μM (PTP1B). Compound 26 was revealed to be a mix-type inhibitor on α-glucosidase and a noncompetitive-type inhibitor on PTP1B based on enzyme kinetic study. Furthermore, compound 42 could selectively inhibited PTP1B as a mix-type inhibitor with IC₅₀ value of 134.9 μM, which was 2.5-fold higher than the positive control, suramin sodium (IC₅₀ 339.0 μM), but not inhibit α-glucosidase.

SUBMITTER: Yang XT

PROVIDER: S-EPMC8749348 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Natural Product Ginsenoside 20(S)-25-Methoxyl-Dammarane-3?, 12?, 20-Triol in Cancer Treatment: A Review of the Pharmacological Mechanisms and Pharmacokinetics.

Project description:Panax ginseng has been used as an herbal medicine for thousands of years. Most of its pharmacological effects are attributed to its constituent ginsenosides, including 20(S)-25-methoxyl-dammarane-3?, 12?, 20-triol (20(S)-25-OCH3-PPD), which is one of the protopanaxadiol type ginsenosides. It has been found to exhibit anticancer effects by interacting with multiple pharmacological pathways, such as the Wnt/?-catenin, MDM2, ERK/MAPK, and STAT3 signaling pathways. However, its therapeutic potential could be limited by its low bioavailability mainly due to its low aqueous solubility. Thus, several studies have been conducted on its pharmacokinetics and its delivery systems, so as to increase its oral bioavailability. In this review, comprehensive information on its varying pharmacological pathways in cancer, as well as its pharmacokinetic behavior and pharmaceutical strategies, is provided. This information would be useful in the understanding of its diverse mechanisms and pharmacokinetics as an anticancer drug, leading to the design of superior 20(S)-25-OCH3-PPD-containing formulations that maximize its therapeutic potential.

| S-EPMC7212460 | biostudies-literature

20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action.

Project description:We recently isolated 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol (25-OCH3-PPD), a natural product from Panax notoginseng, and demonstrated its cytotoxicity against a variety of cancer cells. Here we report the effects of this compound in vitro and in vivo on human prostate cancer cells, LNCaP (androgen-dependent) and PC3 (androgen-independent), in comparison with three structurally related ginsenosides, ginsenoside Rh2, ginsenoside Rg3, and 20(S)-protopanaxadiol. Of the four test compounds, 25-OCH3-PPD was most potent. It decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines. It also decreased the levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cdks 2 and 4) and increased or activated pro-apoptotic proteins (cleaved PARP, cleaved caspase-3, -8, and -9). In LNCaP cells, 25-OCH3-PPD inhibited the expression of the androgen receptor and prostate-specific antigen. Moreover, 25-OCH3-PPD inhibited the growth of prostate cancer xenograft tumours. Combining 25-OCH3-PPD with conventional chemotherapeutic agents or with radiation led to potent antitumour effects; tumour regression was almost complete following administration of 25-OCH3-PPD and either taxotere or gemcitabine. 25-OCH3-PPD also demonstrated low toxicity to noncancer cells and no observable toxicity in animals. In conclusion, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent against both androgen-dependent and androgen-independent prostate cancer.

| S-EPMC2259179 | biostudies-literature

(3S,12R,20S,24R)-20,24-Ep-oxy-dammarane-3,12,25-triol.

Project description:In the title mol-ecule, C(30)H(52)O(4), the three six-membered rings are in chair conformations, the cyclo-pentane ring is in an envelope form and the tetra-hydro-furan ring has a conformation inter-mediate between half-chair and sofa. In the crystal, mol-ecules are linked by inter-molecular O-H?O hydrogen bonds into helical chains along [100]. Two intra-molecular O-H?O hydrogen bonds are also present. One C atom of the tetrahydrofuran ring and its attached H atoms are equally disordered over two sets of sites.

| S-EPMC3213554 | biostudies-other

Regiocontrolled ring opening of monoprotected 2,3-epoxy-1,4-diols using alkynyl aluminum reagents. Synthesis of differentially monoprotected alkynyl triol derivatives.

Project description:The regioselectivity of the epoxide ring opening reaction of cis and trans TIPS-monoprotected 2,3-epoxy-1,4-diols with diethylalkynyl aluminum reagents was studied. Alane and alanate conditions in toluene or dichloromethane were explored. The alkynyl attack at the C2 epoxide carbon was favored for both, the alane and alanate conditions in toluene, while in dichloromethane the C3 attack was preferred. The best regioselectivities were obtained using the alanate conditions in toluene. This methodology provides access to differentially monoprotected alkynyl triols with high diastereoselectivity. These compounds are useful building bocks for polypropionate synthesis and are precursors for the introduction of the hydroxymethyl moiety found in some polyketide systems.

| S-EPMC4852392 | biostudies-literature

Anti-Diabetic Activity of 2,3,6-Tribromo-4,5-Dihydroxybenzyl Derivatives from Symphyocladia latiuscula through PTP1B Downregulation and α-Glucosidase Inhibition.

Project description:The marine alga, Symphyocladia latiuscula (Harvey) Yamada, is a good source of bromophenols with numerous biological activities. This study aims to characterize the anti-diabetic potential of 2,3,6-tribromo-4,5-dihydroxybenzyl derivatives isolated from S. latiuscula via their inhibition of tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Additionally, this study uses in silico modeling and glucose uptake potential analysis in insulin-resistant (IR) HepG2 cells to reveal the mechanism of anti-diabetic activity. This bioassay-guided isolation led to the discovery of three potent bromophenols that act against PTP1B and α-glucosidase: 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether) (3). All compounds inhibited the target enzymes by 50% at concentrations below 10 μM. The activity of 1 and 2 was comparable to ursolic acid (IC50; 8.66 ± 0.82 μM); however, 3 was more potent (IC50; 5.29 ± 0.08 μM) against PTP1B. Interestingly, the activity of 1⁻3 against α-glucosidase was 30⁻110 times higher than acarbose (IC50; 212.66 ± 0.35 μM). Again, 3 was the most potent α-glucosidase inhibitor (IC50; 1.92 ± 0.02 μM). Similarly, 1⁻3 showed concentration-dependent glucose uptake in insulin-resistant HepG2 cells and downregulated PTP1B expression. Enzyme kinetics revealed different modes of inhibition. In silico molecular docking simulations demonstrated the importance of the 7⁻OH group for H-bond formation and bromine/phenyl ring number for halogen-bond interactions. These results suggest that bromophenols from S. latiuscula, especially highly brominated 3, are inhibitors of PTP1B and α-glucosidase, enhance insulin sensitivity and glucose uptake, and may represent a novel class of anti-diabetic drugs.

| S-EPMC6471218 | biostudies-literature

Inhibition of protein tyrosine phosphatase (PTP1B) and ?-glucosidase by geranylated flavonoids from Paulownia tomentosa.

Project description:Protein tyrosine phosphatase 1B (PTP1B) and ?-glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of Paulownia tomentosa fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (1-8) displaying dual inhibition of PTP1B and ?-glucosidase. The isolated compounds were identified as flavanones (1-5) and dihydroflavonols (6-8). Inhibitory potencies of these compounds varied accordingly, but most of the compounds were highly effective against PTP1B (IC50?=?1.9-8.2??M) than ?-glucosidase (IC50?=?2.2-78.9??M). Mimulone (1) was the most effective against PTP1B with IC50?=?1.9??M, whereas 6-geranyl-3,3',5,5',7-pentahydroxy-4'-methoxyflavane (8) displayed potent inhibition against ?-glucosidase (IC50?=?2.2??M). All inhibitors showed mixed type ? inhibition toward PTP1B, and were noncompetitive inhibitors of ?-glucosidase. This mixed type behavior against PTP1B was fully demonstrated by showing a decrease in Vmax, an increase of Km, and Kik/Kiv ratio ranging between 2.66 and 3.69.

| S-EPMC6010085 | biostudies-literature

Effect of a synthetic steroid 5α-androst-3β, 5α, 6β-triol on gene expression in irradiated BV2 cells

Project description:We aimed to study the potential role and underlying mechanism of 5α-androst-3β, 5α, 6β-triol on irradiated BV2 cells. We established radiation induced BV2 cells injury model and pretreated with 5α-androst-3β, 5α, 6β-triol or vehicle. We then performed gene expression profiling analysis using data obtained from RNA-seq of different groups.

2024-04-18 | GSE230636 | GEO

Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B.

Project description:Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors.

| S-EPMC2637956 | biostudies-literature

Properties and Corrosion Resistance Mechanism of a Self-Healing Propane-1,2,3-Triol-Loaded Polysulfone Microcapsule Coating Loaded with Epoxy Resin.

Project description:Propane-1,2,3-triol-loaded polysulfone (PSF) microcapsules were prepared by the solvent evaporation method. The particle size of the microcapsules is about 140 μm. The shell wall thickness is about 17 μm approximately. The microcapsules have high thermal stability and antiwear performance. The self-healing coating was prepared by adding the prepared capsule into the epoxy resin coating. After electrochemical and corrosion immersion experiments, the resistance modulus of the coating added to the microcapsules was higher than the others in a 3.5 wt % NaCl corrosion solution, and it had the lowest corrosion current density, so the self-healing microcapsule coatings showed excellent healing ability and corrosion inhibition function for microcracks. This was attributed to the formation of a hydrophobic film after propane-1,2,3-triol was released from the damaged microcapsules.

| S-EPMC9245092 | biostudies-literature

Arylsulfonyl histamine derivatives as powerful and selective ?-glucosidase inhibitors.

Project description:A series of simple N-arylbenzenesulfonyl histamine derivatives were prepared and screened against ?-glucosidase. Inhibition was in the micromolar range for several N ?,N ?-di-arylsulfonyl compounds, with N ?,N ?-di-4-trifluorobenzenesulfonyl histamine (IId) being the best inhibitor. Compound IId is a reversible and competitive ?-glucosidase inhibitor, and presented good selectivity with respect to other target enzymes, including ?-glucosidase and ?-amylase, and interesting predicted physicochemical properties. Docking studies have been run to postulate ligand-enzyme interactions to account for the experimental results. In vivo, compound IId produced a similar hypoglycemic effect to acarbose with half of its dose.

| S-EPMC7489258 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data