Macrophages/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol against Experimental Intracerebral Hemorrhage in Mice DOI
Jidong Sun,

Chen Pu,

Erwan Yang

et al.

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 17, 2022

Abstract Intracerebral hemorrhage (ICH) is a devasting stroke type with high mortality and disability. Inflammatory response induced by macrophages/microglia (M/Ms) activation one of the leading causes brain damage after ICH. The anti-inflammatory effects resveratrol (RSV) have already been evaluated in several models central nervous system disease. Therefore, we designed current study to assess role RSV ICH explore its downstream mechanism related Sirt3. autologous artery blood injection was administrated create an mouse model. M/Ms specific Sirt3 knockout f/f ; CX3CR1-Cre (Sirt3 cKO) used evaluate on treatment. Neuronal function hematoma volume were assessed indicate damage. pro-inflammatory marker (CD16) cytokine (TNF-α) measured inflammatory effects. Our results showed that treatment alleviates neurological deficits, reduces apoptosis, increases clearance day 7 In addition, effectively suppressed CD16 + decreased TNF-α release. cKO mice, protective abolished, indicating potential partially due signaling activation. could be promising candidate therapeutic agent for target inhibit inflammation.

Language: Английский

Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases DOI
Hossein Mousavi, Mehdi Rimaz, Behzad Zeynizadeh

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(9), P. 1828 - 1881

Published: April 22, 2024

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a–h), hydrazine monohydrate (NH2NH2•H2O) for regioselective preparation some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a–h). After synthesis characterization mentioned cinnolines (3a–h), in silico multi-targeting inhibitory properties these heterocyclic scaffolds investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2(G2019S), hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, hDHODH, which confirmed their functions roles neurodegenerative (NDs), based on molecular docking studies, obtained results were compared with wide range approved drugs well-known (with IC50, EC50, etc.) compounds. addition, ADMET prediction analysis was performed examine prospective drug synthesized compounds The from studies ADMET-related data demonstrated that series heteroaryl)-5,6-dihydrobenzo[h]cinnolines especially hit ones, can really be turned into potent core new treatment and/or due having reactionable locations, they able further organic reactions (such as cross-coupling reactions), expansion (for example, using other types monohydrates) makes avenue designing novel efficient purpose.

Language: Английский

Citations

9
Engineered urinary-derived extracellular vesicles loaded nanoenzymes as Trojan horses to regulate the inflammatory microenvironment for treatment of Alzheimer's disease DOI

Zetai Bai,

Kezhen Ge,

Jingjing Fu

et al.

Chemical Engineering Journal, Journal Year: 2023, Volume and Issue: 465, P. 142955 - 142955

Published: April 15, 2023

Language: Английский

Citations

15
Novel neuroprotective pyromeconic acid derivatives with concurrent anti-Aβ deposition, anti-inflammatory, and anti-oxidation properties for treatment of Alzheimer's disease DOI
Xueyan Liu, Chuanyu Yu, Yuxing Yao

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 248, P. 115120 - 115120

Published: Jan. 13, 2023

Language: Английский

Citations

11
Novel potent and selective dual acetylcholinesterase inhibitors: N-substituted theobromine and theophylline derivatives DOI
Brunella Biscussi, Eduardo J. Cueto‐Díaz, Concepción Pérez

et al.

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

New caffeine analogues, derived from theobromine and theophylline, exhibit potent selective acetylcholinesterase inhibition, positioning them as promising lead compounds for the development of novel drugs targeting neurodegenerative diseases.

Language: Английский

Citations

0
Rh(III)-Catalyzed Redox-Neutral C–H Activation/Annulation of Oxadiazolones with Sulfoxonium Ylides to access oxadiazoloisoquinolinone DOI

Pothapragada S. K. Prabhakar Ganesh,

Eswaran Kamaraj,

Vairaperumal Veeramani

et al.

New Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Oxadiazolone-fused isoquinolines were synthesized via Rh( iii )-catalyzed [4+2] annulation and C–H activation, followed by acymethylation products with antidiabetic anti-inflammatory potential.

Language: Английский

Citations

0
Systematic Analysis and Prediction of the Target Space of Bioactive Food Compounds: Filling the Chemobiological Gaps DOI
Andrés Sánchez-Ruiz, Gonzalo Colmenarejo

Journal of Chemical Information and Modeling, Journal Year: 2022, Volume and Issue: 62(16), P. 3734 - 3751

Published: Aug. 8, 2022

Food compounds and their molecular interactions are crucial for health provide new chemotypes targets drug nutraceutic design. Here, we retrieve analyze the complete set of published food with human proteins using FooDB as a compound ChEMBL source interactions. The data analyzed in terms 19 target classes classes, showing small fraction assignment (1.6%) unraveling multiple gaps chemobiological space these molecules. By well-established cheminformatic approaches [similarity ensemble approach (SEA) combined maximum Tanimoto coefficient to nearest bioactive, "SEA + TC"], achieve much enhanced (64.2%), filling many hypothesis fast focused testing. publishing sets analyses, expect resources speed up full clarification compounds, opening opportunities

Language: Английский

Citations

13
Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice DOI
Jidong Sun,

Chen Pu,

Erwan Yang

et al.

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(6), P. 2871 - 2882

Published: Feb. 14, 2023

Language: Английский

Citations

8
Nature as a source and inspiration for human monoamine oxidase B (hMAO-B) inhibition: A review of the recent advances in chemical modification of natural compounds DOI
Francesco Melfi, Simone Carradori, Andrea Angeli

et al.

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 18(8), P. 851 - 879

Published: June 19, 2023

Over the past 5 years, we have witnessed intense research activity about biological potential of natural products (NPs) as human monoamine oxidase B (hMAO-B) inhibitors. Despite promising inhibitory activity, compounds often suffer from pharmacokinetic lissues, such poor aqueous solubility, extensive metabolism, and low bioavailability.This review provides an overview current landscape NPs selective hMAO-B inhibitors highlights their use a starting scaffold to design (semi)synthetic derivatives overcome therapeutic (pharmacodynamic pharmacokinetic) limitations obtain more robust structure-activity relationships (SARs) for each scaffold.All scaffolds herein presented displayed broad chemical diversity. The knowledge enzyme allows positive correlations associated with consumption specific food or possible herb-drug interactions suggests Medicinal Chemists how address functionalization potent compounds.

Language: Английский

Citations

8
Design, Synthesis and Biological Evaluation of Galantamine Analogues for Cognitive Improvement in Alzheimer's Disease DOI
Mengzhen Li, Chao Ma,

Yao Li

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 284, P. 117198 - 117198

Published: Dec. 24, 2024

Language: Английский

Citations

2
Multiplatform-Integrated Identification of Melatonin Targets for a Triad of Psychosocial-Sleep/Circadian-Cardiometabolic Disorders DOI Open Access
Luciana Aparecida Campos, Ovidiu Constantin Baltatu, Sergio Senar

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(1), P. 860 - 860

Published: Jan. 3, 2023

Several psychosocial, sleep/circadian, and cardiometabolic disorders have intricately interconnected pathologies involving melatonin disruption. Therefore, we hypothesize that could be a therapeutic target for treating potential comorbid diseases associated with this triad of psychosocial-sleep/circadian-cardiometabolic disorders. We investigated melatonin's prediction tractability The the proposed disorder was using databases from Europe PMC, ChEMBL, Open Targets Genetics, Phenodigm, PheWAS. association scores receptors MT1 MT2 were explored evidence target-disease predictions. as tractable in managing supervised machine learning to identify activities cardiovascular, neuronal, metabolic assays at cell, tissue, organism levels curated ChEMBL database. Target-disease visualization done by graphs created "igraph" library-based scripts displayed Gephi ForceAtlas algorithm. combined PMC (data type: text mining), drugs), Genetics Portal genetic associations), PhenoDigm animal models), PheWAS associations) yielded types varying melatonin-disease correlations. Of databases, 235 targeted greater than 0.2; classify per disease class: 37% listed psychosocial disorders, 9% sleep/circadian 54% Using learning, 546 or experimental predicted measured activity identified 248 registered trials, 144 phase I IV trials agonists been completed, which 33.3% 59.7% 6.9% Melatonin's druggability evidenced evaluating While research development is more advanced, scores, substantial on discovery cardiovascular supports continued R&D scores. A multiplatform analysis provided an integrative assessment investigations may justify further translational research.

Language: Английский

Citations

5