Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and Anti-Inflammatory Activities of Phloroglucinol-Based Derivatives.

ABSTRACT: The natural product phloroglucinol-based derivatives representing monoacyl-, diacyl-, dimeric acyl-, alkylated monoacyl-, and the nitrogen-containing alkylated monoacylphloro- glucinols were synthesized and evaluated for inhibitory activities against the inflammatory mediators such as inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-?B). The diacylphloroglucinol compound 2 and the alkylated acylphloroglucinol compound 4 inhibited iNOS with IC50 values of 19.0 and 19.5 µM, respectively, and NF-?B with IC50 values of 34.0 and 37.5 µM, respectively. These compounds may serve as leads for the synthesis of more potent anti-inflammatory compounds for future drug discovery.

SUBMITTER: Li N

PROVIDER: S-EPMC6321231 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and Anti-Inflammatory Activities of Phloroglucinol-Based Derivatives.

Li Ning N Khan Shabana I SI Qiu Shi S Li Xing-Cong XC

Molecules (Basel, Switzerland) 20181207 12

The natural product phloroglucinol-based derivatives representing monoacyl-, diacyl-, dimeric acyl-, alkylated monoacyl-, and the nitrogen-containing alkylated monoacylphloro- glucinols were synthesized and evaluated for inhibitory activities against the inflammatory mediators such as inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-κB). The diacylphloroglucinol compound 2 and the alkylated acylphloroglucinol compound 4 inhibited iNOS with IC50 values ...[more]

PMID: 30544542

Similar Datasets

Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives.

Project description:Pyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20S-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxinol oxidation metabolite, and its anti-inflammatory activity was assessed using an NO inhibition assay. Interestingly, the dehydrogenation at C-12 of pyxinol derivatives improved their potency greatly. Furthermore, half of the derivatives exhibited better NO inhibitory activity than hydrocortisone sodium succinate, a glucocorticoid drug. The structure-activity relationship analysis indicated that the kinds of amino acid residues and their hydrophilicity influenced the activity to a great extent, as did R/S stereochemistry at C-24. Of the various derivatives, 5c with an N-Boc-protected phenylalanine residue showed the highest NO inhibitory activity and relatively low cytotoxicity. Moreover, derivative 5c could dose-dependently suppress iNOS, IL-1β, and TNF-α via the MAPK and NF-κB pathways, but not the GR pathway. Overall, pyxinol derivatives hold potential for application as anti-inflammatory agents.

| S-EPMC9921557 | biostudies-literature

Design, synthesis and in vivo anti-inflammatory activities of 2,4-diaryl-5-4H-imidazolone derivatives.

Project description:A series of 2,4-diaryl-5(4H)-imidazolones were prepared and evaluated for their anti-inflammatory activities. Some selected 2,4-diaryl-5(4H)-imidazolones exhibited excellent anti-inflammatory activity in the carrageenan-induced rat paw edema model. Structure Activity Relationships within the series were studied. The substitution at the N-sulfonamide moiety by a small hydrophilic acetyl group resulted in compounds with superior in vivo anti-inflammatory properties. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 3-day treatment of 25 mg/kg/day.

| S-EPMC6268676 | biostudies-literature

Anti-glycation, Carbonyl Trapping and Anti-inflammatory Activities of Chrysin Derivatives.

Project description:The aim of this study was searching anti-glycation, carbonyl trapping and anti-inflammatory activities of chrysin derivatives. The inhibitory effect of chrysin on advanced glycation end-products (AGEs) was investigated by trapping methylglyoxal (MGO), and MGO-conjugated adducts of chrysin were analyzed using LC-MS/MS. The mono- or di-MGO-conjugated adducts of chrysin were present at 63.86 and 29.69% upon 48 h of incubation at a chrysin:MGO ratio of 1:10. The MGO adducted positions on chrysin were at carbon 6 or 6 & 8 in the A ring by classic aldol condensation. To provide applicable knowledge for developing chrysin derivatives as AGE inhibitors, we synthesized several O-alkyl or ester derivatives of chrysin and compared their AGE formation inhibitory, anti-inflammatory, and water solubility characteristics. The results showed that 5,7-di-O-acetylchrysin possessed higher AGE inhibitory and water solubility qualities than original chrysin, and retained the anti-inflammation activity. These results suggested that 5,7-di-O-acetylchrysin could be a potent functional food ingredient as an AGE inhibitor and anti-inflammatory agent, and promotes the development of the use of chrysin in functional foods.

| S-EPMC6099615 | biostudies-literature

Synthesis of 2,4-Diaminopyrimidine Core-Based Derivatives and Biological Evaluation of Their Anti-Tubercular Activities.

Project description:Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level. In the current study, we designed and synthesized a series of mt-DHFR inhibitors that contain a 2,4-diaminopyrimidine core with side chains to occupy the glycerol binding site with proper hydrophilicity for cell entry, and tested their anti-tubercular activity against Mtb H37Ra. Among them, compound 16l showed a good anti-TB activity (MIC = 6.25 ?g/mL) with a significant selectivity against vero cells. In the molecular simulations performed to understand the binding poses of the compounds, it was noticed that only side chains of a certain size can occupy the glycerol binding site. In summary, the novel synthesized compounds with appropriate side chains, hydrophobicity and selectivity could be important lead compounds for future optimization towards the development of future anti-TB drugs that can be used as monotherapy or in combination with other anti-TB drugs or antibiotics. These compounds can also provide much information for further studies on mt-DHFR. However, the enzyme target of the compounds still needs to be confirmed by pure mt-DHFR binding assays.

| S-EPMC6151568 | biostudies-literature

Synthesis, antidiabetic, antioxidant and anti-inflammatory activities of novel hydroxytriazenes based on sulpha drugs.

Project description:The present study is aimed to investigate the anti-inflammatory, antioxidant and antidiabetic activities of three series of hydroxytriazenes based on sulfa drugs viz; Sulphathiazole (ST), Sulfisoxazole (SF) and Sulphamethoxazole (SM). Antidiabetic activities of the synthesized hydroxytriazenes were investigated by α-glucosidase and α-amylase inhibition method and IC50 values were recorded. The compounds presented significant α-glucosidase and α-amylase inhibition effect with IC50 values ranging from 122 to 341 μg/mL. Anti-inflammatory activity was also investigated by carrageenan-induced paw edema (CPE) method, where % inhibition was up to 89% after 4 h of treatment and antioxidant properties of the similar compounds were assessed by DPPH and ABTS radical scavenging assays. Antioxidant capacity of all the hydroxytriazenes detected by ABTS assay, was significantly higher as compared to DPPH assay. The hydroxytriazenes having highest antioxidant capacity presented IC50 values for compound ST-1 and ST-6 are 488 μg/mL for DPPH, 54.12 μg/mL for ABTS and 858.5 μg/mL for DPPH, 48.0 μg/mL for ABTS, respectively. These results suggested that ABTS assay may be more useful than DPPH assay for synthetic antioxidants. The findings from the molecular docking experiments may also expand the formation of new potent sulpha drugs based hydroxytriazenes targeting towards the subunit of C-terminal of human maltase-glucoamylase for the treatment of diabetes metabolic disorder. Overall, highlight the multifunctional role of hydroxytriazenes as antidiabetic, antioxidant and anti-inflammatory agents.

| S-EPMC7472862 | biostudies-literature

Synthesis, Anti-Inflammatory and Anti- Nociceptive Activities and Cytotoxic Effect of Novel Thiazolidin-4-ones Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors.

Project description:OBJECTIVE(S):Nowadays, COX - 2 inhibitors such as valdecoxib are removed from the market because of their cardiovascular toxicity and their potential to increase the risk of strokes. In response to this, medicinal chemists have attempted to synthesize new classes of COX-2 Inhibitors. MATERIALS AND METHODS:In this study, three novel analogues of thiazolidin-4-ones derivatives 2a-c were synthesized. The ability of these compounds to inhibit ovine COX-1 and COX-2 (0.2- 0.8 µM) was determined using a colorimetric method. The cytotoxic effect of the synthesized compounds (25-100 M) was also investigated by measuring their cytotoxicity against Caco-2 and MCF-7 cell lines using MTT assay. Cell apoptosis was determined by ?ow cytometry. Writhing test (7.5-75 mg/kg) was used to examine the antinociceptive effects in mice. The effect of the analogues against acute inflammation (7.5-75 mg/kg) was also studied using xylene-induced ear edema test in mice. RESULTS:The synthesized compounds showed a weak capacity to inhibit the proliferation of Caco-2 and MCF-7 cell lines. The COX-2 inhibition potency and selectivity index for test compounds 2a-b were as follows; celecoxib > 2b > 2a. On the other hand, all three analogues exhibited strong antinociceptive activity against acetic acid-induced writhing. The anti-inflammatory and antinociceptive effects of the analogues were markedly more than positive control, celecoxib. CONCLUSION:This study demonstrates that the antinociceptive and anti-inflammatory activity profiles exhibited by the novel synthesized compounds are independent from their COX-2 inhibitory potencies. The found antinociceptive and anti-inflammatory effects can be caused by interaction with other target; independent from COX-2. Accordingly, the compounds 2a-c could serve as lead compounds to develop novel anti-inflammation and antinociceptive drugs.

| S-EPMC3933800 | biostudies-literature

Antifungal Agents: Design, Synthesis, Antifungal Activity and Molecular Docking of Phloroglucinol Derivatives.

Project description:Pseudoaspidinol is a phloroglucinol derivative with Antifungal activity and is a major active component of Dryopteris fragrans. In our previous work, we studied the total synthesis of pseudoaspidinol belonging to a phloroglucinol derivative and investigated its antifungal activity as well as its intermediates. However, the results showed these compounds have low antifungal activity. In this study, in order to increase antifungal activities of phloroglucinol derivatives, we introduced antifungal pharmacophore allylamine into the methylphloroglucinol. Meanwhile, we remained C1⁻C4 acyl group in C-6 position of methylphloroglucinol using pseudoaspidinol as the lead compound to obtain novel phloroglucinol derivatives, synthesized 17 compounds, and evaluated antifungal activities on Trichophyton rubrum and Trichophyton mentagrophytes in vitro. Molecular docking verified their ability to combine the protein binding site. The results indicated that most of the compounds had strong antifungal activity, in which compound 17 were found to be the most active on Trichophyton rubrum with Minimum Inhibitory Concentration (MIC) of 3.05 μg/mL and of Trichophyton mentagrophytes with MIC of 5.13 μg/mL. Docking results showed that compounds had a nice combination with the protein binding site. These researches could lay the foundation for developing antifungal agents of clinical value.

| S-EPMC6321598 | biostudies-literature

New pentadienone oxime ester derivatives: synthesis and anti-inflammatory activity.

Project description:To develop novel anti-inflammatory agents, a series of new pentadienone oxime ester compounds were designed and synthesized. The structures were determined by IR, 1H NMR, 13 C NMR, and HRMS. All compounds have been screened for their anti-inflammatory activity by evaluating their inhibition against LPS-induced nitric oxide (NO) release in RAW 264.7 cell. Among them, compound 5j was found to be one of the most potent compounds in inhibiting NO and IL-6 (IC50 values were 6.66 µM and 5.07 µM, respectively). Preliminary mechanism studies show that title compound 5j could significantly suppress expressions of nitric oxide synthase, COX-2, and NO, IL-6 through Toll-like receptor 4/mitogen-activated protein kinases/NF-κB signalling pathway. These data support further studies to assess rational design of more efficient pentadienone oxime ester derivatives with anti-inflammatory activity in the future.

| S-EPMC6010105 | biostudies-literature

Antioxidative and Anti-Inflammatory Activities of Galloyl Derivatives and Antidiabetic Activities of Acer ginnala.

Project description:Chromatographic isolation of the 80% MeOH extract of Acer ginnala (AG) yielded seven galloyl derivatives: gallic acid (1), ginnalin B (2), acertannin (3), maplexin D (4), maplexin E (5), quercetin-3-O-(2''-galloyl)-α-L-rhamnopyranoside (6), and kaempferol-3-O-(2''-galloyl)-α-L-rhamnopyranoside (7). This is the first study to report the isolation of compounds 4 and 5 from AG. Galloyl derivatives 3-7 exhibited potent radical scavenging activities, with 5 and 7 showing particularly strong inhibitory activities against nitric oxide production in lipopolysaccharides- (LPS-) stimulated RAW264.7 cells. In addition, oral administration of AG extract (500 mg/kg b.w.) improved symptoms of hyperglycemia and blunted the increases in serum GOT/GPT levels in a rat model of streptozotocin-induced diabetes. These results suggest that galloyl derivatives (1-7) are antioxidant and anti-inflammatory agents and that AG extract has potential as a functional material or novel herbal medicine for treating diabetes mellitus.

| S-EPMC5352893 | biostudies-literature

Novel ?, ?-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities.

Project description:Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel ?, ?-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR) analysis indicated that introduction of ?, ?-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.

| S-EPMC6150263 | 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