A5024129015- Cancer therapeutics and mechanisms
- Synthesis and biological activity
- Synthesis and Biological Evaluation
- Click Chemistry and Applications
- Antifungal resistance and susceptibility
- Bioactive Compounds and Antitumor Agents
- Fungal Infections and Studies
- Lung Cancer Research Studies
- Photodynamic Therapy Research Studies
- Cancer-related Molecular Pathways
- Nanoplatforms for cancer theranostics
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Neutropenia and Cancer Infections
- Fluorine in Organic Chemistry
- Protein Degradation and Inhibitors
- Quinazolinone synthesis and applications
- Microbial Natural Products and Biosynthesis
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Pneumocystis jirovecii pneumonia detection and treatment
- Asymmetric Synthesis and Catalysis
- Synthesis and bioactivity of alkaloids
- Phytochemical compounds biological activities
- Synthetic Organic Chemistry Methods
South China Normal University
2024-2025
Second Military Medical University
2015-2024
Changhai Hospital
2013
East China University of Science and Technology
2013
University of New Mexico
2013
Xichang University
2007
A critical question in natural product-based drug discovery is how to translate the product into drug-like molecules with optimal pharmacological properties. The generation of product-inspired scaffold diversity an effective but challenging strategy investigate broader chemical space and identify promising leads. Extending our efforts evodiamine, a diverse library containing 11 evodiamine-inspired novel scaffolds their derivatives were designed synthesized. Most them showed good excellent...
In a continuing effort to develop highly potent azole antifungal agents, the three-dimensional quantitative structure−activity relationship methods, CoMFA and CoMSIA, were applied using set of novel compounds. The binding mode compounds at active site lanosterol 14α-demethylase was further explored flexible docking method. Various hydrophobic, van der Waals, π−π stacking, hydrogen bonding interactions observed between azoles enzyme. Based on results from molecular modeling, receptor-based...
Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus . Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, library novel bearing various substitutions or modified scaffold were synthesized. Among them, number showed substantial increase antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly...
Human topoisomerase I (TopoI) is recognized as a valuable target for the development of effective antitumor agents. Structure-based virtual screening was applied to discovery structurally diverse TopoI inhibitors. From 23 compounds selected by screening, total 14 were found be Five hits (compounds 1, 14, 20, 21, and 23) also showed moderate good in vitro activity. These novel structures can considered starting points new lead compounds. Hit 20 (evodiamine) chosen preliminary...
The p53-MDM2 interaction has been proved to be a valuable target develop effective antitumor agents. Novel inhibitors bearing pyrrolidone scaffolds were successfully identified by structure-based design. nanomolar inhibitor 5 possessed good inhibitory activity (K(i) = 780 nM) due its hydrophobic and hydrogen bonding interactions with MDM2. Further hit optimization led the discovery of number highly potent derivatives improved in vitro antiproliferative potency. Compounds 41 260.0 60a 150.0...
An organocatalytic enantioselective Michael–Michael cascade reaction is developed for the synthesis of chiral spirotetrahydrothiopyrans. This highly functionalized scaffold was assembled in moderate to good yield (55–74%) and excellent diastereo- enantioselectivities (>30:1 dr, ≥ 99% ee) with creation four consecutive stereogenic centers. The novel spiro-oxindole validated as a new class p53-MDM2 protein–protein interaction inhibitors antitumor activity.
Cryptococcus neoformans is one of the most important causes life-threatening fungal infections in immunocompromised patients. Lanosterol 14 alpha-demethylase (CYP51) target azole antifungal agents. This study describes, for first time, 3-dimensional model CYP51 from (CnCYP51). The was further refined by energy minimization and molecular-dynamics simulations. active site CnCYP51 well characterized multiple-copy simultaneous-search calculations, four functional regions rational drug design...
Abstract A powerful divergent cascade strategy has been explored for the easy construction of diverse enantioenriched pyrazole‐derived scaffolds from readily available chiral fused pyrazole‐tetrahydropyran acetals. These versatile intermediates can react in various ways to give Michael–aldol, reduction–lactonization, α‐hydroxylation–acetalization–oxidation, and Wittig–aldol Wittig–oxa‐Michael reactions. Using only six simple building blocks, these processes gave five distinct molecular...
Designing multitarget drugs remains a significant challenge in current antitumor drug discovery. Because of the synergistic effect between topoisomerase and HDAC inhibitors, present study reported first-in-class triple inhibitors I/II HDAC. On basis 3-amino-10-hydroxylevodiamine SAHA, series hybrid molecules was successfully designed synthesized. In particular, compound 8c proven to be potent inhibitor with good antiproliferative apoptotic activities. This proof-of-concept also validated...
p53-Murine double minute 2 (MDM2) interaction and histone deacetylases (HDACs) are important targets in antitumor drug development. Inspired by the synergistic effects between MDM2 HDACs, first MDM2/HDACs dual inhibitors were identified, which showed excellent activities against both targets. In particular, compound 14d was proven to be a potent orally active MDM2/HDAC inhibitor, whose mechanisms validated cancer cells. Compound vivo potency A549 xenograft model, providing promising lead for...
The development of novel photosensitizer with high phototoxicity, low dark toxicity, and good water solubility is a challenging task for photodynamic therapy (PDT). A series chlorin p6-based water-soluble amino acid conjugates were synthesized investigated antitumor activity. Among them, aspartylchlorin p6 dimethylester (7b) showed highest phototoxicity against melanoma cells weakest which was more phototoxic than verteporfin while less toxicity. It also exhibited better in vivo PDT efficacy...
A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum activity. Particularly, compound C38 comparable in vitro activity to fluconazole without toxicity human embryonic lung cells. It also exhibited good fungicidal against both fluconazole-sensitive -resistant Candida albicans cells had potent inhibition biofilm formation hyphal growth. Moreover, synergistic combination with (FLC) FLC-resistant species. Preliminary mechanism studies...
Background and Purpose Necroptosis is a form of programmed, caspase‐independent, cell death, mediated by receptor‐interacting protein kinases, RIPK1 RIPK3, the mixed lineage kinase domain‐like (MLKL). contributes to pathophysiology various inflammatory, infectious, degenerative diseases. Thus, identification low MW inhibitors for necroptosis has broad therapeutic relevance. Here, we identified that pan‐Raf inhibitor TAK‐632 was also an necroptosis. We have further generated more selective,...
Abstract Hard carbon (HC) is regarded as the leading anode material for sodium ion batteries (SIBs), owing to its low storage potential, high reversible specific capacity, abundant precursor sources, and cost‐effectiveness. Nevertheless, randomly oriented amorphous structure large number of defects in HC result initial Coulombic efficiency, inadequate rate performance, limited cycling stability when utilized an SIBs. Therefore, optimizing microstructure obtain both a defect ratio transport...