Browse
Submit Data
Databases
API
Help

Dataset Information

41 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and biological evaluation of 2-arylbenzofuran derivatives as potential anti-Alzheimer's disease agents.

ABSTRACT: Alzheimer's disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and β-secretase inhibitory activity. The IC₅₀ value of compound 20 against acetylcholinesterase inhibition (0.086 ± 0.01 µmol·L^-1) is similar to donepezil (0.085 ± 0.01 µmol·L^-1) and is better than baicalein (0.404 ± 0.04 µmol·L^-1). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 ± 0.03 µmol·L^-1). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD.

SUBMITTER: Yun Y

PROVIDER: S-EPMC8765280 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Synthesis and biological evaluation of 3-arylbenzofuranone derivatives as potential anti-Alzheimer's disease agents.

Project description:Multi-target drugs can better address the cascade of events involved in oxidative stress and the reduction in cholinergic transmission that occur in Alzheimer's disease than cholinesterase inhibitors alone. We synthesised a series of 3-arylbenzofuranone derivatives and evaluated their antioxidant activity, cholinesterase inhibitory activity, and monoamine oxidase inhibitory activity. 3-Arylbenzofuranone compounds exhibit good antioxidant activity as well as selective acetylcholinesterase inhibitory activity. The IC50 value of anti-acetylcholinesterase inhibition of Compound 20 (0.089 ± 0.01 μM) is similar to the positive drug donepezil (0.059 ± 0.003 μM). According to the experimental results, Compounds 7, 13 show a certain effect in the in vitro evaluation performed and have the potential as drug candidates for the treatment of Alzheimer's disease.

| S-EPMC7155212 | biostudies-literature

Synthesis and biological evaluation of 3-(4-aminophenyl)-coumarin derivatives as potential anti-Alzheimer's disease agents.

Project description:The work is focused on the design of drugs that prevent and treat Alzheimer's disease (AD) and its complications. A series of 3-(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 ± 0.011 µM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 ± 0.017 µM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications.

| S-EPMC6534212 | biostudies-literature

Synthesis and Biological Evaluation of Thalidomide Derivatives as Potential Anti-Psoriasis Agents.

Project description:Several thalidomide derivatives were synthesized and evaluated for their anti-inflammatory activity. Introduction of the benzyl group to the parent thalidomide is unfavorable in which 2-(1-benzyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (4a) was inactivated. However, the inhibitory activities on TNF-? and IL-6 expression in HaCaT cells were improved by the substitution of a chloro- or methoxy- group at the phenyl position of 4a. The IL-6 inhibitory activity decreased in an order of 5c (69.44%) > 4c (48.73%) > 6c (3.19%) indicating the 3-substituted derivative is more active than the 4-substituted counterpart, which in turn is more active than the 2-substituted counterpart. Among them, 2-[1-(3-chlorobenzyl)-2,6-dioxopiperidin-3-yl]isoindoline-1,3-dione (5c) was found to inhibit TNF-? and IL-6 expression in HaCaT cells with a higher potency than thalidomide and no significant cell cytotoxicity was detected at 10 ?M. In psoriasis, Compound 5c reduced IL-6, IL-8, IL-1? and IL-24 in imiquimod-stimulated models. Our results indicated that compound 5c is a potential lead of novel anti-psoriasis agents. Structural optimization of compound 5c and its in vivo assay are ongoing.

| S-EPMC6212999 | biostudies-literature

Synthesis and biological evaluation of 3-arylcoumarin derivatives as potential anti-diabetic agents.

Project description:A variety of substituted 3-arylcoumarin derivatives were synthesised through microwave radiation heating. The method has characteristics of environmental friendliness, economy, simple separation, and purification process, less by-products and high reaction yield. Those 3-arylcoumarin derivatives were screened for antioxidant, ?-glucosidase inhibitory and advanced glycation end-products (AGEs) formation inhibitory. Most compounds exhibited significant antioxidant and AGEs formation inhibitory activities. Anti-diabetic activity studies showed that compounds 11 and 17 were equipotent to the standard drug glibenclamide in vivo. According to the experimental results, the target compound 35 can be used as a lead compound for the development of new anti-diabetic drugs. The whole experiment showed that anti-diabetic activity is prevalent in 3-arylcoumarins, which added a new natural skeleton to the development of anti-diabetic active drugs.

| S-EPMC6211316 | biostudies-literature

Synthesis and Biological Evaluation of Novel Selenyl and Sulfur-l-Dopa Derivatives as Potential Anti-Parkinson's Disease Agents.

Project description:Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons at level of substantianigrapars compacta. To date, there is no cure for this pathology, except for some drugs able to alleviate the symptoms of PD. In this paper we report the synthesis and biological evaluation of novel sulfur- and selenyl-l-Dopa (LD) derivatives (SP1-6) obtained through the amide junction between the amino group of LD and carboxylic moiety of sulfur- and selenyl-organic compounds, which are commercially available. Biological activity was evaluated on human undifferentiated and retinoic acid/phorbol myristyl acetate (RA/PMA)-differentiated SY-SH5Y neuroblastoma cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activity against oxidative stress was measured using nitroblue tetrazolium (NBT) and 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assays. Finally, physico-chemical characterization and plasma stability studies of SP1-6 were also performed. Biological data revealed that SP6 has a significant protective action against the neurotoxic action of 6-hydroxydopamine (6-OHDA) and H2O2 in a RA/PMA-differentiated SY-SH5Y neuroblastoma cell line that proved to be an effective antioxidant and protective compound. SP6, endowed with a lipophilic nature, low molecular weight, and plasma stability, can easily cross biological membranes via passive diffusion such as through the blood-brain barrier. SP6 has great potential for developing novel pharmacological approach for neurodegenerative diseases, such as PD. Further studies will help define its exact antioxidant mechanism and determine whether the neuroprotective action is mediated or modulated by glutathione peroxidase (GPx).

| S-EPMC6628379 | biostudies-literature

2,5-Diketopiperazine Derivatives as Potential Anti-Influenza (H5N2) Agents: Synthesis, Biological Evaluation, and Molecular Docking Study.

Project description:2,5-Diketopiperazine derivatives, consisting of benzylidene and alkylidene substituents at 3 and 6 positions, have been considered as a core structure for their antiviral activities. Herein, the novel N-substituted 2,5-Diketopiperazine derivatives were successfully prepared and their antiviral activities against influenza virus were evaluated by monitoring viral propagation in embryonated chicken eggs. It was found that (3Z,6Z)-3-benzylidene-6-(2-methyl propylidene)-4-substituted-2,5-Diketopiperazines (13b-d), (3Z,6E)-3-benzylidene-6-(2-methylpropyli dene)-1-(1-ethyl pyrrolidine)-2,5-Diketopiperazine (14c), and Lansai-C exhibited negative results in influenza virus propagation at a concentration of 25 µg/mL. Additionally, molecular docking study revealed that 13b-d and 14c bound in 430-cavity of neuraminidase from H5N2 avian influenza virus and the synthesized derivatives also strongly interacted with the key amino acid residues, including Arg371, Pro326, Ile427, and Thr439.

| S-EPMC9268516 | biostudies-literature

Synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents.

Project description:To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the "combination principle" in drug discovery. The ligustrazine derivatives' anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (4) and 3 ?,12 ?-dihydroxy-5?-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5) not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD?? value of the compound 5 exceeded 3.0 g/kg by oral administration in mice.

| S-EPMC6268357 | biostudies-literature

Synthesis and biological activity evaluation of novel peroxo-bridged derivatives as potential anti-hepatitis B virus agents.

Project description:Previous studies have demonstrated that natural steroid compounds containing a peroxide bridge exhibited potential anti-hepatitis B virus activity. To continue our research, a simple and regioselective methodology, using Eosin Y as a clean photosensitized oxidation catalyst, was developed for the synthesis of a peroxide bridge in steroids. The method that using Eosin Y as the catalyst was exposed to visible light and furbished in high yields, did not involve tedious work-up or purification, and avoided using environmentally hazardous solvents. It can be regarded as a green protocol. Moreover, a series of cholesterol and ?-sitosterol derivatives containing a peroxide bridge were synthesized using this method and screened for their anti-HBV activity. Among the compounds synthesized in this research, 5?,8?-cyclicobioxygen-6-vinyl-3-oxo-cholesterone (1f, 3.13 ?g ml-1) had the most potent activity with inhibition rates of 77.45% ± 6.01% and 58.73% ± 8.64% on the secretion of HBsAg and HBeAg antigens, respectively, after 8 days. Further acute toxicity test showed that the LD50 value of compound 1f was 362.46 mg kg-1 after an intraperitoneal injection in mice. Moreover, structure-activity relationships of cholesterol and ?-sitosterol derivatives were briefly discussed.

| S-EPMC6072307 | biostudies-literature

Synthesis and biological evaluation of ursolic acid derivatives bearing triazole moieties as potential anti-Toxoplasma gondii agents.

Project description:Ursolic acid (UA), a plant-derived compound, has many properties beneficial to health. In the present study, we synthesised three series of novel UA derivatives and evaluated their anti-Toxoplasma gondii activity both in vitro and in vivo. Most derivatives exhibited an improved anti-T. gondii activity in vitro when compared with UA (parent compound), whereas compound 3d exhibited the most potent anti-T. gondii activity in vivo. Spiramycin served as the positive control. Additionally, determination of biochemical parameters, including the liver and spleen indexes, indicated compound 3d to effectively reduce hepatotoxicity and significantly enhance anti-oxidative effects, as compared with UA. Furthermore, our molecular docking study indicated compound 3d to possess a strong binding affinity for T. gondii calcium-dependent protein kinase 1 (TgCDPK1). Based on these findings, we conclude that compound 3d, a derivative of UA, could act as a potential inhibitor of TgCDPK1.

| S-EPMC6407578 | biostudies-literature

Design, Synthesis, Molecular Modelling, and Biological Evaluation of Oleanolic Acid-Arylidene Derivatives as Potential Anti-Inflammatory Agents.

Project description:IntroductionOleanolic acid, a pentacyclic triterpenic acid, is widely distributed in medicinal plants and is the most commonly studied triterpene for various biological activities, including anti-allergic, anti-cancer, and anti-inflammatory.MethodsThe present study was carried out to synthesize arylidene derivatives of oleanolic acid at the C-2 position by Claisen Schmidt condensation to develop more effective anti-inflammatory agents. The derivatives were screened for anti-inflammatory activity by scrutinizing NO production inhibition in RAW 264.7 cells induced by LPS and their cytotoxicity. The potential candidates were further screened for inhibition of LPS-induced interleukin (IL-6) and tumour necrosis factor-alpha (TNF-α) production in RAW 264.7 cells.ResultsThe results of in vitro studies revealed that derivatives 3d, 3e, 3L, and 3o are comparable to that of the oleanolic acid on the inhibition of TNF-α and IL-6 release. However, derivative 3L was identiﬁed as the most potent inhibitor of IL-6 (77.2%) and TNF-α (75.4%) when compared to parent compound, and compounds 3a (77.18%), 3d (71.5%), and 3e (68.8%) showed potent inhibition of NO than oleanolic acid (65.22%) at 10µM. Besides, from docking score and Cyscore analysis analogs (3e, 3L, 3n) showed greater affinity towards TNF-α and IL-1β than dexamethasone.ConclusionHerein, we report a series of 15 new arylidene derivatives of oleanolic acid by Claisen Schmidt condensation reaction. All the compounds synthesized were screened for their anti-inﬂammatory activity against NO, TNF-α and IL-6. From the data, it was evident that most of the compounds exhibited better anti-inﬂammatory activity.

| S-EPMC7871991 | 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