A5076473559- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
- Bioactive Compounds and Antitumor Agents
- Synthesis and biological activity
- Cancer-related Molecular Pathways
- Adenosine and Purinergic Signaling
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- RNA modifications and cancer
- Click Chemistry and Applications
- Synthesis and Biological Evaluation
- Ubiquitin and proteasome pathways
- Microbial Natural Products and Biosynthesis
- interferon and immune responses
- Genomics, phytochemicals, and oxidative stress
- MicroRNA in disease regulation
- Nanoplatforms for cancer theranostics
- Redox biology and oxidative stress
- Sirtuins and Resveratrol in Medicine
- Pharmacogenetics and Drug Metabolism
- Research on Leishmaniasis Studies
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Peptidase Inhibition and Analysis
- Protein Tyrosine Phosphatases
University of Kentucky
2013-2023
Markey Cancer Center
2011-2023
University of Kentucky HealthCare
2021
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....
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...
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...
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...
Abstract Developing effective treatments for colorectal cancers through combinations of small-molecule approaches and immunotherapies present intriguing possibilities managing these otherwise intractable cancers. During a broad-based, screening effort against multiple cancer cell lines, we identified indole-substituted quinolines (ISQ), such as N7,N7-dimethyl-3-(1-methyl-1H-indol-3-yl)quinoline-2,7-diamine (ISQ-1), potent in vitro inhibitors several lines. We found that ISQ-1 inhibited Wnt...
Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and requires new therapeutic strategies to improve clinical outcomes. EOC metastasizes in abdominal cavity through dissemination peritoneal fluid ascites, efficiently adapt nutrient-deprived microenvironment, resist current chemotherapeutic agents. Accumulating evidence suggests that mitochondrial oxidative phosphorylation critical for adaptation cells this otherwise hostile microenvironment. Although...
Amino-substituted coumarins undergo Pictet–Spengler condensations with 3-ketosteroids to afford spirocyclic androgens for the study 17-oxidoreductases intracrine, androgen metabolism.
Fluorinated, phenylethynyl-substituted heterocycles that possessed either an N-methylamino or N,N-dimethylamino group attached to including pyridines, indoles, 1H-indazoles, quinolines, and isoquinolines inhibited the proliferation of LS174T colon cancer cells in which inhibition cyclin D1 induction cyclin-dependent kinase inhibitor-1 (i.e., p21Wif1/Cip1) served as a readout for antineoplastic activity at cellular level. On molecular level, these agents, particularly...
<div>Abstract<p>Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and requires new therapeutic strategies to improve clinical outcomes. EOC metastasizes in abdominal cavity through dissemination peritoneal fluid ascites, efficiently adapt nutrient-deprived microenvironment, resist current chemotherapeutic agents. Accumulating evidence suggests that mitochondrial oxidative phosphorylation critical for adaptation cells this otherwise...
<p>Supplementary Information</p>
<p>Supplementary Information</p>
<div>Abstract<p>Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and requires new therapeutic strategies to improve clinical outcomes. EOC metastasizes in abdominal cavity through dissemination peritoneal fluid ascites, efficiently adapt nutrient-deprived microenvironment, resist current chemotherapeutic agents. Accumulating evidence suggests that mitochondrial oxidative phosphorylation critical for adaptation cells this otherwise...
<div>Abstract<p>Developing effective treatments for colorectal cancers through combinations of small-molecule approaches and immunotherapies present intriguing possibilities managing these otherwise intractable cancers. During a broad-based, screening effort against multiple cancer cell lines, we identified indole-substituted quinolines (ISQ), such as...
<p>Supplementary methods and figures</p>
<p>Supplementary methods and figures</p>
<div>Abstract<p>Developing effective treatments for colorectal cancers through combinations of small-molecule approaches and immunotherapies present intriguing possibilities managing these otherwise intractable cancers. During a broad-based, screening effort against multiple cancer cell lines, we identified indole-substituted quinolines (ISQ), such as...
Abstract In an effort to screen natural compounds and their derivatives as novel agents for cancer treatment, we developed two semisynthetic nature compounds, A14 A52, which have potencies in vitro cell proliferation studies against LS174T PC-3 cells the mid-nanomolar range. inhibited more than 90% of around 300 nM also vivo prostate xenografts nude mice. Cell morphology comparisons with known antineoplastic suggested that disrupted microtubule organization. tubulin polymerization assay this...