A5002402103- Wnt/β-catenin signaling in development and cancer
- Synthesis and Reactions of Organic Compounds
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Synthesis of Organic Compounds
- Cancer therapeutics and mechanisms
- Fluorine in Organic Chemistry
- Cancer-related Molecular Pathways
- Microbial Natural Products and Biosynthesis
- Synthesis and biological activity
- Synthesis and Characterization of Heterocyclic Compounds
- Cancer Mechanisms and Therapy
- Cancer-related gene regulation
- PI3K/AKT/mTOR signaling in cancer
- Bioactive Compounds and Antitumor Agents
- Synthesis and Biological Evaluation
- Bioactive natural compounds
- Skin and Cellular Biology Research
- RNA modifications and cancer
- Estrogen and related hormone effects
- Beetle Biology and Toxicology Studies
- Carbohydrate Chemistry and Synthesis
- Sirtuins and Resveratrol in Medicine
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Crystallization and Solubility Studies
University of Kentucky
2014-2024
Hebei Normal University
2021-2023
Markey Cancer Center
2011-2021
National Academy of Sciences of Ukraine
2004-2006
Botryococcene biosynthesis is thought to resemble that of squalene, a metabolite essential for sterol metabolism in all eukaryotes. Squalene arises from an initial condensation two molecules farnesyl diphosphate (FPP) form presqualene (PSPP), which then undergoes reductive rearrangement squalene. In principle, botryococcene could arise alternative the intermediate. Because these proposed similarities, we predicted synthase would squalene and hence isolated synthase-like genes Botryococcus...
Methionine S-adenosyltransferase 2A (MAT2A) is the catalytic subunit for synthesis of S-adenosylmethionine (SAM), principal methyl donor in many biological processes. MAT2A up-regulated cancers, including liver cancer and colorectal (CRC) a potentially important drug target. We developed family fluorinated N,N-dialkylaminostilbene agents, called FIDAS that inhibit proliferation CRC cells vitro vivo. Using biotinylated analogue, we identified as direct exclusive binding target these agents....
Inhibition of the catalytic subunit heterodimeric methionine S-adenosyl transferase-2 (MAT2A) with fluorinated N,N-dialkylaminostilbenes (FIDAS agents) offers a potential avenue for treatment liver and colorectal cancers where upregulation this enzyme occurs. A study structure-activity relationships led to identification most active compounds as those (1) either 2,6-difluorostyryl or 2-chloro-6-fluorostyryl subunit, (2) an N-methylamino N,N-dimethylamino group attached in para orientation...
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in United States. CRC initiated by mutations tumor suppressor gene, adenomatous polyposis coli (APC), or β-catenin gene. These stabilize and constitutively activate Wnt/β-catenin target genes, such as c-Myc cyclin D1, ultimately to cancer. Naturally occurring stilbene derivatives, resveratrol pterostilbene, inhibit Wnt signaling repress cell proliferation but are ineffective at concentrations less than 10 μM. To...
Cytisine-linked isoflavonoids (CLIFs) inhibit cancer cells by targeting the peroxisomal enzyme HSD17B4.
Abstract The regioselective condensations of various 7‐hydroxyisoflavonoids with bis( N , ‐dimethylamino)methane in a Mannich reaction provided C‐8 ‐dimethylaminomethyl‐substituted isoflavonoids good yield. Similar 7‐hydroxy‐8‐methylisoflavonoids led to the C‐6‐substituted analogs. Thermal eliminations dimethylamine from these C‐6 or generated ortho ‐quinone methide intermediates within isoflavonoid frameworks for first time. Despite other potential competing outcomes, trapped dienophiles...
C-6 and C-8 Hydroxy-, acetoxy- alkoxymethyl derivatives of isoflavones were synthesized from Mannich bases show inhibition in the low micromolar range a prostate cancer PC3 cell line.
The importance of upregulated Wnt signaling in colorectal cancers led to efforts develop inhibitors that target β-catenin this pathway. We now report several "Wnt inhibitors" allegedly actually function as mitochondrial proton uncouplers independently activate AMPK and concomitantly inhibit signaling. As expected for a process which uncoupling diminishes ATP production, uncoupler, FCCP, glucose metabolic inhibitor, 2-DG, activated inhibited Also consistent with these findings, well-known...
Abstract Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of ( Z )-2-benzylidene-6-hydroxybenzofuran-3(2 H )-one scaffold that possessed low nanomolar vitro potency cell proliferation assays using various cancer lines, vivo prostate PC-3 xenograft and zebrafish models, selectivity for colchicine-binding site on tubulin, absence appreciable toxicity. Among leading, biologically active analogs were )-2-((2-((1-ethyl-5-methoxy-1...
Aberrant activation of Wnt signaling triggered by mutations in either Adenomatous Polyposis Coli (APC) or CTNNB1 (β-catenin) is a hallmark colorectal cancers (CRC). As part program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing aryl heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors the pathway. A biotinylated variant N-((5-chloro-8-hydroxyquinolin-7-yl)...
Alternative pre-mRNA splicing is a central element of eukaryotic gene expression. Its deregulation can lead to disease, and methods change splice site selection are developed as potential therapies. Spinal muscular atrophy caused by the loss SMN1 (survival motoneuron 1) gene. A therapeutic avenue for spinal treatment promote exon 7 inclusion almost identical SMN2 2) The factor tra2-beta1 promotes this antagonized protein phosphatase (PP) 1. To identify new compounds that inclusion, we...
Purpose Triple negative breast cancer (TNBC) is the most lethal and aggressive subtype of cancer. AMP-activated protein kinase (AMPK) a major energy regulator that suppresses tumor growth, 1-(3-chloro-4-((trifluoromethyl)thio)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea (FND-4b) novel AMPK activator inhibits growth induces apoptosis in colon The purpose this project was to test effects FND-4b on activation, proliferation, with particular emphasis TNBC. Materials methods (i) Estrogen-receptor...
The aminomethylation of hydroxylated isoflavones with 2-aminoethanol, 3-amino-1-propanol, 4-amino-1-butanol, and 5-amino-1-pentanol in the presence excess formaldehyde led principally to 9-(2-hydroalkyl)-9,10-dihydro-4H,8H-chromeno[8,7-e][1,3]-oxazin-4-ones 4 and/or tautomeric 7-hydroxy-8-(1,3-oxazepan-3-ylmethyl)-4H-chromen-4-ones 5. ratio these tautomers was dependent on solvent polarity, electronic effects aryl substituents isoflavone structure amino alcohol. NMR studies confirmed...
Advanced prostate tumors usually metastasize to the lung, bone, and other vital tissues are resistant conventional therapy. Prostate apoptosis response-4 protein (Par-4) is a tumor suppressor that causes in therapy-resistant cancer cells by binding specifically receptor, Glucose-regulated protein-78 (GRP78), found only on surface of cells. 3-Arylquinolines or "arylquins" induce normal release Par-4 from intermediate filament protein, vimentin promote secretion targets paracrine manner. A...
Vimentin is an intermediate filament (IF) protein that expressed in leukocytes, fibroblasts and endothelial cells of blood vessels. filaments contribute to structural stability the cell membrane, organelle positioning transport. self-assembles into a dimer subsequently forms high-order structures, including tetramers octamers. The details IF assembly at crystallographic resolutions are limited tetrameric form. We describe crystal structure fragment vimentin rod domain (coil 1B) with...
A reliable method for the synthesis of B-ring hydroxylated homoisoflavonoids and 3-hetarylmethyl chromones has been developed. The involves an initial oxa-Diels–Alder reaction ortho-quinone methides generated from aryl/hetaryl-substituted ortho-(N,N-dimethylaminomethyl)phenols with (2E)-3-(N,N-dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-ones subsequent cascade reactions. This synthetic strategy avoids conventional multistep protocols does not require protection hydroxyl groups, thus...
Leishmaniasis, a disease caused by protozoa of the Leishmania species, afflicts roughly 12 million individuals worldwide. Most existing drugs for leishmaniasis are toxic, expensive, difficult to administer, and subject drug resistance. We report new class antileishmanial leads, 3-arylquinolines, that potently block proliferation intramacrophage amastigote form parasites with good selectivity relative host macrophages. Early lead 34 was rapidly acting possessed potency against L. mexicana...