A5074235217- Phosphodiesterase function and regulation
- Asymmetric Synthesis and Catalysis
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and Catalytic Reactions
- Chemical synthesis and alkaloids
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- Pulmonary Hypertension Research and Treatments
- Synthesis of Indole Derivatives
- X-ray Diffraction in Crystallography
- Axial and Atropisomeric Chirality Synthesis
- Catalytic C–H Functionalization Methods
- Organic and Inorganic Chemical Reactions
- Medicinal Plants and Neuroprotection
- Synthetic Organic Chemistry Methods
- Synthesis of heterocyclic compounds
- Peptidase Inhibition and Analysis
- Bioactive natural compounds
- Computational Drug Discovery Methods
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Enzyme function and inhibition
- Advanced Condensed Matter Physics
- Sulfur-Based Synthesis Techniques
- Chemical Synthesis and Reactions
- Oxidative Organic Chemistry Reactions
Sun Yat-sen University
2014-2025
Hainan University
2021-2025
General Hospital of Shenyang Military Region
2024
Hubei Cancer Hospital
2023
East China University of Science and Technology
2007-2016
National Research Institute of Brewing
2016
University of Amsterdam
2014
University of New Mexico
2011
Shanghai Institute of Materia Medica
2007
Chinese Academy of Sciences
2007
Significance Drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from virtual screening existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. It has been demonstrated that approach accelerated free energy perturbation-based absolute binding (FEP-ABFE) predictions can reach an unprecedentedly high rate, leading to successful identification 15 potent inhibitors SARS-CoV-2...
Abstract Metachronous liver metastases (MLM) are characterised by high incidence and mortality in clinical colorectal cancer treatment. Currently traditional methods cannot effectively predict prevent the occurrence of metachronous metastasis cancer. Based on 5hmC‐Seal analysis blood tissue samples, this study found that portal venous was more relevant to tumour gDNA than peripheral blood. We performed a novel epigenetic liquid biopsy strategy using 10 5hmC alterations, accurately...
N6-methyladenosine (m6A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass obesity-associated protein (FTO), the first identified m6A demethylase, cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, bioassay. As a result, two namely 18077 18097 were identified, which can selectively inhibit demethylase activity FTO. Specifically, bound to active site then inhibited cell cycle...
Nitro-charged activation: An organocatalytic enantioselective conjugate addition of aryl methyl nucleophiles to enals has been developed produce ubiquitous chiral benzylic building blocks (see scheme; TES=triethylsilyl). Taking advantage the strongly electron-withdrawing nature nitro groups, which can be conveniently transformed into other functionalities, this functionality was incorporated aromatic systems as a temporary activating group.
In 3D topological insulators achieving a genuine bulk-insulating state is an important research topic. Recently, the material system (Bi,Sb)$_{2}$(Te,Se)$_{3}$ (BSTS) has been proposed as insulator with high resistivity and low carrier concentration (Ren \textit{et al.} \cite{Ren2011}). Here we present study to further refine properties of BSTS. We have synthesized Bi$_{2-x}$Sb${_x}$Te$_{3-y}$Se$_{y}$ single crystals compositions around $x = 0.5$ $y 1.3$. Resistance Hall effect measurements...
Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility difficulty total synthesis limited its application therapeutic agent. To tackle these challenges, NOB was synthesized high yield by concise route six steps fourteen derivatives were with remarkable efficacy. All compounds showed sensitivity to paclitaxel (PTX)...
Abstract Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available other diseases and, thus, repurpose them of In general, drug repurposing effort new disease, such as COVID-19, usually starts virtual screening drugs, followed experimental...
The development of dual prostaglandin E
Psoriasis is a complex chronic inflammatory disease that severely affects the quality of life patients. However, current medications could only control symptoms but not cure psoriasis with unmet medical needs. Herein, structure-based optimizations natural product moracin M (IC50 2.9 μM) led to novel PDE4 inhibitor L30 greatly improved potency 8.6 nM) and remarkable selectivity across other PDEs families (>201-fold). The binding pattern revealed by cocrystal structure was different from...
An enantioselective Michael addition of ketones to alkylidenemalononitriles catalyzed by chiral primary amine I with (R)-5c as a co-catalyst in good yields (>90%) and enantioselectivities (85-96% ee) has been developed. The strategy also extended three-component version through domino Knoevenagel/Michael sequence similar or better outcomes.
Phosphodiesterase-2A (PDE2A) is a potential therapeutic target for treatment of Alzheimer's disease and pulmonary hypertension. However, most the current PDE2A inhibitors have moderate selectivity over other PDEs. In present study, we described discovery novel by structure-based virtual screening combining pharmacophore model screening, molecular docking, dynamics simulations, bioassay validation. Nine hits out 30 molecules from SPECS database (a hit rate 30%) inhibited with affinity less...
Nowadays, small-molecule drugs have become an indispensable part of tumor immunotherapy. Accumulating evidence has indicated that specifically blocking PGE2/EP4 signaling to induce robust antitumor immune response represents attractive immunotherapy strategy. Herein, a 2H-indazole-3-carboxamide containing compound 1 was identified as EP4 antagonist hit by screening our in-house library. Systematic structure–activity relationship exploration leads the discovery 14, which displayed...
Phosphodiesterase 5 (PDE5) inhibitors have been used as clinical agents to treat erectile dysfunction and pulmonary arterial hypertension (PAH). Herein, we detail the discovery of a novel series chromeno[2,3-c]pyrrol-9(2H)-one derivatives selective orally bioavailable against phosphodiesterase 5. Medicinal chemistry optimization resulted in 2, which exhibits desirable inhibitory potency 5.6 nM with remarkable selectivity well excellent pharmacokinetic properties an oral bioavailability...
Discovery of multitarget-directed ligands (MTDLs), targeting different factors simultaneously to control the complicated pathogenesis Alzheimer's disease (AD), has become an important research area in recent years. Both phosphodiesterase 9A (PDE9A) and butyrylcholinesterase (BuChE) inhibitors could participate processes AD attenuate neuronal injuries improve cognitive impairments. However, on MTDLs combining inhibition PDE9A BuChE not been reported yet. In this study, a series novel...
Optimization efforts were devoted to discover novel PDE10A inhibitors in order improve solubility and pharmacokinetics properties for a long-term therapy against pulmonary arterial hypertension (PAH) starting from the previously synthesized inhibitor A. As result, potent highly selective inhibitor, 14·3HCl (half maximal inhibitory concentration, IC50 = 2.8 nmol/L >3500-fold selectivity) exhibiting desirable metabolic stability with remarkable bioavailability of 50% was identified aid...
An efficient bifunctional cinchona alkaloid derived thiourea-promoted enantioselective conjugate addition of nitroalkanes to indolylidenecyanoacetates has been developed under neat conditions. The process leads synthetically interesting densely functionalized 3,3′-disubstituted oxindoles with creation up three stereogenic centers.
To further explore the structure–activity relationship around chromeno[2,3-c]pyrrol-9(2H)-one scaffold, 19 derivatives as inhibitors against PDE5 were discovered. The most potent inhibitor 3 has an IC50 of 0.32 nM with remarkable selectivity and druglike profile. Oral administration (1.25 mg/kg) caused comparable therapeutic effects to sildenafil (10.0 pulmonary arterial hypertension. Further, different binding patterns from revealed in cocrystal structures, which provide structural...
Type 2 diabetes mellitus (T2DM) is a metabolic disease and major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP-4), serine protease, has been rapidly emerging as an effective therapeutic target for treatment T2DM. In this study, series of novel DPP-4 inhibitors, featuring pyrazole-3-carbohydrazone scaffold, have discovered using integrated approach structure-based virtual screening, chemical synthesis, bioassay. Virtual screening SPECS Database, followed by...
Abstract An organocatalytic enantioselective Friedel–Crafts alkylation of 1‐naphthols with isatins has been developed. The process is catalyzed by a simple cinchona alkaloid derived thiourea and gives biologically interesting, enantioenriched 3‐(naphthalen‐2‐yl)‐3‐hydroxy‐2‐oxindoles in moderate to good yields 42–83 % high enantioselectivity up 94 ee . Furthermore, an unexpected intramolecular dehydration reaction proceeds spontaneously 4‐substituted offer structurally different ketone oxindoles.
Phosphodiesterase 10 (PDE10) inhibitors have received much attention as promising therapeutic agents for central nervous system (CNS) disorders such schizophrenia and Huntington's disease. Recently, a hit compound 1 with novel chromone scaffold has shown moderate inhibitory activity against PDE10A (IC50 = 500 nM). Hit-to-lead optimization resulted in 3e an improved 6.5 nM), remarkable selectivity (>95-fold over other PDEs), good metabolic stability (RLM t1/2 105 min) by using integrated...