A5101483874- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Synthesis and bioactivity of alkaloids
- RNA Interference and Gene Delivery
- Crystallization and Solubility Studies
- Synthesis and Biological Evaluation
- RNA and protein synthesis mechanisms
- Berberine and alkaloids research
- X-ray Diffraction in Crystallography
- Natural product bioactivities and synthesis
- Cancer therapeutics and mechanisms
- Alkaloids: synthesis and pharmacology
- Fungal Biology and Applications
- Biological Activity of Diterpenoids and Biflavonoids
- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Analysis
- Skin and Cellular Biology Research
- Crystallography and molecular interactions
- Phytochemical compounds biological activities
- Hair Growth and Disorders
- Chromatography in Natural Products
- Quinazolinone synthesis and applications
- Wnt/β-catenin signaling in development and cancer
- Phytochemistry and Biological Activities
- Chemical synthesis and alkaloids
Purdue University West Lafayette
2017-2024
China Pharmaceutical University
2022-2024
State Key Laboratory of Natural Medicine
2022-2024
Ningxia Medical University
2024
Qinghai Red Cross Hospital
2023
Shenyang Pharmaceutical University
2014-2022
Northeast Agricultural University
2021
Institute of Earth Environment
2020
Chinese Academy of Sciences
2020
Center for Cancer Research
2018
Peganumine A (1), a new dimeric β-carboline alkaloid characterized by unique 3,9-diazatetracyclo[6.5.2.01,9.03,8]pentadec-2-one scaffold, was isolated from the seeds of Peganum harmala. The structure including absolute configuration determined spectroscopic data, X-ray crystallography, ECD calculation, and CD exciton chirality approaches. Compound 1 showed moderate cytotoxic activity against MCF-7, PC-3, HepG2 cells selective effects on HL-60 with an IC50 value 5.8 μM.
Abstract Human telomeres can form DNA G‐quadruplex (G4), an attractive target for anticancer drugs. telomeric G4s bear inherent structure polymorphism, challenging understanding specific recognition by ligands or proteins. Protoberberines are medicinal natural‐products known to stabilize and inhibit telomerase. Here we report epiberberine (EPI) specifically recognizes the hybrid‐2 G4 predominant in physiologically relevant K + solution converts other forms hybrid‐2, first such example...
MYC is one of the most important oncogenes and overexpressed in majority cancers. G-Quadruplexes are noncanonical four-stranded DNA secondary structures that have emerged as attractive cancer-specific molecular targets for drug development. The G-quadruplex formed proximal promoter region oncogene (MycG4) has been shown to be a transcriptional silencer amenable small-molecule targeting suppression. Indenoisoquinolines human topoisomerase I inhibitors clinical testing with improved...
In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by (1)H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed most potential activity. Subsequently, NMR- bioassay-guided isolation P. was performed obtain four pairs partially racemized β-carboline alkaloids, pegaharmines A-D (1-4). Their structures absolute configurations were determined extensive analyses, X-ray crystallography, ECD calculations, CD exciton...
Aberrant expression of PDGFR-β is associated with a number diseases. The G-quadruplexes (G4s) formed in gene promoter are transcriptional modulators and amenable to small molecule targeting. major G4 the was previously shown have broken G-strand. Herein, we report that sequence forms vacancy G-quadruplex (vG4) which can be filled stabilized by physiologically relevant guanine metabolites, such as dGMP, GMP, cGMP, well guanine-derivative drugs. We determined NMR structure dGMP-fill-in vG4 K+...
Abstract KRAS is one of the most highly mutated oncoproteins, which overexpressed in various human cancers and implicated poor survival. The G-quadruplex formed oncogene promoter ( -G4) a transcriptional modulator amenable to small molecule targeting. However, no available -G4-ligand complex structure has yet been determined, seriously hinders structure-based rational design -G4 targeting drugs. In this study, we report NMR solution structures bulge-containing bound berberine coptisine,...
Two pairs of enantiomeric alkaloid dimers, (±)-macleayins A (1) and B (2), representing a novel dimerization pattern two different types alkaloids via C–C σ-bond, were isolated from the aerial parts Macleaya cordata. The separation was achieved by chiral chromatography. Their structures stereochemistry determined analysis extensive spectroscopic data, electronic circular dichroism calculation, single-crystal X-ray diffraction data. (−)-Macleayin exhibits modest cytotoxic activity against...
Investigation of the alkaloids from Peganum harmala seeds yielded two pairs unique racemic pyrroloindole alkaloids, (±)-peganines A–B (1–2); rare thiazole derivatives, peganumals (3–4); six new β-carboline pegaharmines F–K (5–10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, single-crystal X-ray diffraction. Notably, incorporation pyrrole indole moieties in peganines A–B, fragments a C-1...
Pegaharmalines A (1) and B (2), two novel β-carboline alkaloids with unprecedented carbon skeletons, were isolated from the seeds of Peganum harmala. Their structures determined by spectroscopic methods absolute configuration 1 was elucidated CD analysis. 2 exhibited significant cytotoxicities on HL-60 cells IC50 values 9.4 13.6 μM, respectively.
Two nonbiaryl axially chiral β-carboline-quinazoline dimers, pegaharmols A (1) and B (2), were isolated from the roots of Peganum harmala. Their planar structures elucidated by spectroscopic methods high-resolution mass spectrometry 1D 2D nuclear magnetic resonance (NMR). The stereochemistry was established a comparison between experimental data NMR electronic circular dichroism computed quantum mechanical calculations. It is discovered for first time that β-carboline at C-8 position bonded...
Guanine (G)-oxidation to 8-oxo-7,8-dihydroguanine (OG) by reactive oxygen species in genomic DNA has been implicated with various human diseases. G-quadruplex (G4)-forming sequences gene promoters are highly susceptible G-oxidation, which can subsequently cause activation. However, the underlying G4 structural changes that result from OG modifications remain poorly understood. Herein, we investigate effect of G-oxidation on BLM promoter G4. For first time, show induce a G-vacancy-containing...
Inspired by the intriguing structures and bioactivities of dimeric alkaloids, 11 new thalifaberine-type aporphine-benzylisoquinoline thalicultratines A–K, a tetrahydroprotoberberine-aporphine alkaloid, thalicultratine L, five known ones were isolated from roots Thalictrum cultratum. Their defined on basis NMR HRESIMS data. The antiproliferative activities compounds 1–17 evaluated against human leukemia HL-60 prostate cancer PC-3 cells. Most alkaloids showed potent cytotoxicity selected...
The G-quadruplexes (G4s) formed in the
EGFR tyrosine kinase inhibitors have made remarkable success in targeted cancer therapy. However, therapeutic resistance inevitably occurred and EGFR-targeting therapy has been demonstrated to limited efficacy or utility glioblastoma, colorectal cancer, hepatocellular carcinoma. Therefore, there is a high demand for the development of new targets inhibit signaling. Herein, we found that oncogene proximal promoter sequence forms unique type snap-back loop containing G-quadruplex (G4), which...
Two prenylated biflavonoids, podoverines B–C, were isolated from the dried roots and rhizomes of Sinopodophyllum emodi using a Sephadex LH-20 column (SLHC) high-speed counter-current chromatography (HSCCC). The 95% ethanol extract was partitioned with ethyl acetate in water. Target compounds fraction further enriched purified by combined application SLHC HSCCC. n-Hexane–ethyl acetate–methanol–water (3.5:5:3.5:5, v/v) chosen as two phase solvent system. flow rate mobile optimized at 2.0...
G-quadruplexes are four-stranded nucleic acid secondary structures of biological significance and have emerged as an attractive drug target. The G4 formed in the MYC promoter (MycG4) is one most studied small-molecule targets, a model system for parallel that prevalent DNA G4s RNA G4s. Molecular docking has become essential tool structure-based discovery protein also increasingly applied to DNA. However, DNA, particular G4, binding sites differ significantly from targets. Here we perform...
Persister cells (PS) selected for anticancer therapy have been recognized as a significant contributor to the development of treatment-resistant malignancies. It is found that imposing glutamine restriction induces generation PS, which paradoxically bestows heightened resistance treatment by activating integrated stress response and initiating general control nonderepressible 2-activating transcription factor 4-alanine, serine, cysteine-preferring transporter 2 (GCN2-ATF4-ASCT2) axis....
Four new phenolic compounds, vitexnegheteroins A–D (1–4), were isolated from the seeds of Vitex negundo var. heterophylla, together with eight known compounds. Their structures established on basis extensive 1D and 2D NMR experiments, as well their mass spectroscopic data. The absolute configuration compound 4 was determined by comparing its experimental CD spectrum that calculated time-dependent density functional theory (TDDFT) method. antioxidant anti-inflammatory activities these...