Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Unusual Bicyclo[3.2.1]Octanoid Neolignans from Leaves of Piper crocatum and Their Effect on Pyruvate Dehydrogenase Activity.

ABSTRACT: Three undescribed bicyclo[3.2.1]octanoid neolignan glucosides, along with a known neolignan, were isolated from the leaves of Piper crocatum Ruiz & Pav. Their chemical structures were elucidated using extensive spectroscopic analyses including 1D and 2D NMR experiments and HR-ESI-MS analysis, as well as through comparison with previously reported data. Two compounds were assessed for their inhibitory effect against pyruvate dehydrogenase E1α S300 phosphorylation. The fluorescent image suggested that both compounds (60 µM) revealed a stronger inhibition effect than the positive control (dichloroacetate, DCA 5 mM), with IC₅₀ values of 99.82 µM and 80.25 µM, respectively.

SUBMITTER: Chai YJ

PROVIDER: S-EPMC8469962 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Identification and Evaluation of Apoptosis-Inducing Activity of Ipomone from <i>Ipomoea nil</i>: A Novel, Unusual Bicyclo-[3.2.1] Octanone Containing Gibberic Acid Diterpenoid.

Project description:Ipomone (1), a novel diterpenoid along with seven known compounds (2-8), was isolated for the first time from the acidified hydroalcoholic extract of Ipomoea nil seeds. The structures of the isolated compounds were elucidated via comprehensive NMR spectroscopic data. The absolute configuration of 1 was ascertained through NOESY, NMR, and ECD analyses. Compound 1 was found to contain an unusual bicyclo-[3.2.1] octanone, which appeared first time in any natural product that might be an artifact resulting from the acid-catalyzed 1,2 alkyl shift/rearrangement. The novel compound was screened for cytotoxic activity against a panel of 12 human cancer cell lines and exhibited weak cytotoxicity with IC50 values in the range of 34-86 μM (except for HEK-293 cells). Microscopic studies revealed that compound 1 induced apoptosis and autophagy in A549 cells. To further explore the signaling pathway involved, immunoblot analysis was performed that confirmed inhibition of apoptotic proteins PARP-1 and caspase-3 expression and upregulation of LC3B expression by compound 1. The compound was further subjected to molecular docking studies to evaluate its binding affinity with p110α, PARP-1, and caspase-3 proteins.

| S-EPMC8015099 | biostudies-literature

Synthesis and reactivity of bicyclo[3.2.1]octanoid-derived cyclopropanes.

Project description:Photochemical oxa-di-π-methane rearrangement of bicyclo[3.2.1]octanoid scaffolds affords multifunctional, donor-acceptor cyclopropanes. A related photochemical reaction of an iminium ether substrate uncovered an unprecedented aza-di-π-methane rearrangement of a β,γ-unsaturated iminium. Donor-acceptor cyclopropanes have been evaluated as substrates for reactions generating several new chemotypes.

| S-EPMC3235415 | biostudies-literature

Pirin regulates pyruvate catabolism by interacting with the pyruvate dehydrogenase E1 subunit and modulating pyruvate dehydrogenase activity.

Project description:The protein pirin, which is involved in a variety of biological processes, is conserved from prokaryotic microorganisms, fungi, and plants to mammals. It acts as a transcriptional cofactor or an apoptosis-related protein in mammals and is involved in seed germination and seedling development in plants. In prokaryotes, while pirin is stress induced in cyanobacteria and may act as a quercetinase in Escherichia coli, the functions of pirin orthologs remain mostly uncharacterized. We show that the Serratia marcescens pirin (pirin(Sm)) gene encodes an ortholog of pirin protein. Protein pull-down and bacterial two-hybrid assays followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray ionization-tandem mass spectrometry analyses showed the pyruvate dehydrogenase (PDH) E1 subunit as a component interacting with the pirin(Sm) gene. Functional analyses showed that both PDH E1 subunit activity and PDH enzyme complex activity are inhibited by the pirin(Sm) gene in S. marcescens CH-1. The S. marcescens CH-1 pirin(Sm) gene was subsequently mutated by insertion-deletion homologous recombination. Accordingly, the PDH E1 and PDH enzyme complex activities and cellular ATP concentration increased up to 250%, 140%, and 220%, respectively, in the S. marcescens CH-1 pirin(Sm) mutant. Concomitantly, the cellular NADH/NAD(+) ratio increased in the pirin(Sm) mutant, indicating increased tricarboxylic acid (TCA) cycle activity. Our results show that the pirin(Sm) gene plays a regulatory role in the process of pyruvate catabolism to acetyl coenzyme A through interaction with the PDH E1 subunit and inhibiting PDH enzyme complex activity in S. marcescens CH-1, and they suggest that pirin(Sm) is an important protein involved in determining the direction of pyruvate metabolism towards either the TCA cycle or the fermentation pathways.

| S-EPMC1797226 | biostudies-literature

Synthetic efforts toward the bicyclo[3.2.1]octane fragment of rhodojaponin III.

Project description:Rhodojaponin III is a grayanane-type diterpenoid natural product with a novel chemical scaffold. It shows potent antinociceptive activity and may represent a new class of natural non-opioid analgesics with a novel mode of action. We explored the Au(I)-catalyzed Conia-ene cyclization and the Mn(III)-mediated radical cyclization of alkynyl ketones for the synthesis of the bicyclo[3.2.1]octane fragment of rhodojaponin III. These strategies will be applicable in the synthesis of rhodojaponin III and analogs for future biological studies.

| S-EPMC8153367 | biostudies-literature

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes.

Project description:In order to prepare novel polycyclic derivatives of bicyclo[3.2.1]octadiene systems fused with a thiophene ring, photochemical cyclization and aldol condensation reactions were carried out. The starting substrates were easily obtained by a Vilsmeier-Haack reaction of bicyclo[3.2.1]octadiene thiophene derivatives with dimethylformamide. From the obtained carbaldehydes, novel methyl, methoxy, and cyano-substituted styryl thienobenzobicyclo[3.2.1]octadiene derivatives were synthesized through Wittig reactions and subjected to photochemical cyclization, in terms of obtaining the new annulated structures. As part of this study, the aldol reaction of the starting 2-substituted carbaldehyde with acetone was also performed, which produced the thieno-fused benzobicyclo[3.2.1]octadiene compound with an extended conjugation.

| S-EPMC7277534 | biostudies-literature

Novel Amides Derivative with Antimicrobial Activity of Piper betle var. nigra Leaves from Indonesia.

Project description:Piper betle var. nigra is a tropical plant closely related to the common piper. P. betle has also been dubbed a promising source of natural antioxidants in herbal health products, antibacterial, antifungal, antimalarial, cytotoxic activity against the cancer cell lines K562 and HL-60, and antileishmanial. The aim of this study to observation Antimicrobial activity and isolation of chemical compound. The antimicrobial activity of P. betle extract was performed by well diffusion method against two oral pathogenic bacteria (Streptococcus mutans and Streptococcus sanguinis) and opportunistic pathogenic yeast (Candida albicans). The inoculum (bacterial and yeast suspension) was prepared from a 24-h culture on NB for bacterial suspension and on TSB for yeast suspension. Extraction and isolation using various method of chromatography. Isolated compounds were characterized by spectroscopic means. Our study showed antimicrobial activity from crude ethanol extract of leaves P. betle L. var. nigra against two oral pathogenic bacteria and opportunistic pathogenic yeast with concentration 0.5% and 1%. The first report of two new amides derivatives, piperenamide A (1) and piperenamide B (2) in P. betle L. var. nigra.

| S-EPMC7826617 | biostudies-literature

Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity.

Project description:Sirtuins (SIRTs) are critical enzymes that govern genome regulation, metabolism, and aging. Despite conserved deacetylase domains, mitochondrial SIRT4 and SIRT5 have little to no deacetylase activity, and a robust catalytic activity for SIRT4 has been elusive. Here, we establish SIRT4 as a cellular lipoamidase that regulates the pyruvate dehydrogenase complex (PDH). Importantly, SIRT4 catalytic efficiency for lipoyl- and biotinyl-lysine modifications is superior to its deacetylation activity. PDH, which converts pyruvate to acetyl-CoA, has been known to be primarily regulated by phosphorylation of its E1 component. We determine that SIRT4 enzymatically hydrolyzes the lipoamide cofactors from the E2 component dihydrolipoyllysine acetyltransferase (DLAT), diminishing PDH activity. We demonstrate SIRT4-mediated regulation of DLAT lipoyl levels and PDH activity in cells and in vivo, in mouse liver. Furthermore, metabolic flux switching via glutamine stimulation induces SIRT4 lipoamidase activity to inhibit PDH, highlighting SIRT4 as a guardian of cellular metabolism.

| S-EPMC4344121 | biostudies-literature

E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity.

Project description:The mitochondrial pyruvate dehydrogenase (PDH) complex (PDC) acts as a central metabolic node that mediates pyruvate oxidation and fuels the tricarboxylic acid cycle to meet energy demand. Here, we reveal another level of regulation of the pyruvate oxidation pathway in mammals implicating the E4 transcription factor 1 (E4F1). E4F1 controls a set of four genes [dihydrolipoamide acetlytransferase (Dlat), dihydrolipoyl dehydrogenase (Dld), mitochondrial pyruvate carrier 1 (Mpc1), and solute carrier family 25 member 19 (Slc25a19)] involved in pyruvate oxidation and reported to be individually mutated in human metabolic syndromes. E4F1 dysfunction results in 80% decrease of PDH activity and alterations of pyruvate metabolism. Genetic inactivation of murine E4f1 in striated muscles results in viable animals that show low muscle PDH activity, severe endurance defects, and chronic lactic acidemia, recapitulating some clinical symptoms described in PDC-deficient patients. These phenotypes were attenuated by pharmacological stimulation of PDH or by a ketogenic diet, two treatments used for PDH deficiencies. Taken together, these data identify E4F1 as a master regulator of the PDC.

| S-EPMC5047171 | biostudies-literature

SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells.

Project description:Pyruvate dehydrogenase E1α (PDHA1) is the first component enzyme of the pyruvate dehydrogenase (PDH) complex that transforms pyruvate, via pyruvate decarboxylation, into acetyl-CoA that is subsequently used by both the citric acid cycle and oxidative phosphorylation to generate ATP. As such, PDH links glycolysis and oxidative phosphorylation in normal as well as cancer cells. Herein we report that SIRT3 interacts with PDHA1 and directs its enzymatic activity via changes in protein acetylation. SIRT3 deacetylates PDHA1 lysine 321 (K321), and a PDHA1 mutant mimicking a deacetylated lysine (PDHA1(K321R)) increases PDH activity, compared to the K321 acetylation mimic (PDHA1(K321Q)) or wild-type PDHA1. Finally, PDHA1(K321Q) exhibited a more transformed in vitro cellular phenotype compared to PDHA1(K321R). These results suggest that the acetylation of PDHA1 provides another layer of enzymatic regulation, in addition to phosphorylation, involving a reversible acetyllysine, suggesting that the acetylome, as well as the kinome, links glycolysis to respiration.

| S-EPMC4364304 | biostudies-literature

Constructing chiral bicyclo[3.2.1]octanes via palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes.

Project description:Transition-metal-catalyzed tandem Heck/carbonylation reaction has emerged as a powerful tool for the synthesis of structurally diverse carbonyl molecules, as well as natural products and pharmaceuticals. However, the asymmetric version was rarely reported, and remains a challenging topic. Herein, we describe a palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes. Alcohols, phenols and amines are employed as versatile coupling reagents for the construction of multifunctional chiral bicyclo[3.2.1]octanes with one all-carbon quaternary and two tertiary carbon stereogenic centers in high diastereo- and enantioselectivities. This study represents an important progress in both the asymmetric tandem Heck/carbonylation reactions and enantioselective difunctionalization of internal alkenes.

| S-EPMC7242361 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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