A5003370288- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and biological activity
- Crystal structures of chemical compounds
- Crystallography and molecular interactions
- Synthesis and Biological Evaluation
- Click Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Sesquiterpenes and Asteraceae Studies
- DNA Repair Mechanisms
- Natural product bioactivities and synthesis
- Synthesis of heterocyclic compounds
- Computational Drug Discovery Methods
- Cancer therapeutics and mechanisms
- Synthesis and Reactions of Organic Compounds
- Cannabis and Cannabinoid Research
- Muscle Physiology and Disorders
- RNA Interference and Gene Delivery
- Alzheimer's disease research and treatments
- Neurotransmitter Receptor Influence on Behavior
- Chemical Synthesis and Analysis
- Cholinesterase and Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Quinazolinone synthesis and applications
- Nutrition and Health in Aging
University of Arkansas for Medical Sciences
2013-2023
University of Arkansas at Little Rock
2017
Richard L. Roudebush VA Medical Center
2017
Indiana University – Purdue University Indianapolis
2017
Indiana University School of Medicine
2017
University of Colorado Denver
2015
University of Colorado Anschutz Medical Campus
2015
University of Kentucky
2008-2011
Novel, stable combretastatin-A4 heterocyclic (2<italic>H</italic>)-1,2,3-triazole analogues displayed potent cytotoxic activity against both hematological and solid tumor cell lines with GI<sub>50</sub> values in the low nanomolar range.
A new library of small molecules with structural features resembling combretastatin analogs was synthesized and evaluated for anticancer activity against a panel 60 human cancer cell lines. Three novel acrylonitrile (5, 6 13) caused significant reduction in growth almost all the lines examined, GI50 values generally range 10–100 nM. Based on characteristics similar drugs, we hypothesized that cytotoxic likely due to interaction tubulin. Furthermore, these compounds appeared overcome...
Dengue virus (DENV) causes a variety of difficult‐to‐treat diseases that threaten almost half the world's population. Currently, no effective vaccine or antiviral therapy is available. We have examined series synthetic resveratrol analogs to identify potential anti‐DENV agents. Here, we demonstrate two analogs, PNR‐4‐44 and PNR‐5‐02, possess potent activity with EC 50 values in low nanomolar range. These were shown mainly target viral RNA translation replication, but PNR‐5‐02 also likely...
Abstract Glycogen synthase kinase-3β (GSK3β) controls many physiological pathways, and is implicated in diseases including Alzheimer’s several cancers. GSK3β-mediated phosphorylation of target residues microtubule-associated protein tau (MAPTAU) contributes to MAPTAU hyperphosphorylation subsequent formation neurofibrillary tangles. Inhibitors GSK3β protect against disease are therapeutic for A thiadiazolidinone drug, TDZD-8, a non-ATP-competitive inhibitor targeting with demonstrated...
Novel carbamate (7a–7h) and carbonate (7i, 7j, 8) dimers of melampomagnolide B have been synthesized by reaction the melampomagnolide-B-triazole synthon 6 with various terminal diamino- dihydroxyalkanes. Dimeric products 7b, 7c, 7f exhibited potent growth inhibition (GI50 = 0.16–0.99 μM) against majority cell lines in NCI panel 60 human hematological solid tumor lines. Compound 8 anticancer activity that was 300-fold 1 × 106-fold more cytotoxic than DMAPT, respectively, at a concentration 10...
Novel resveratrol analogues have been synthesized and evaluated for their anticancer activities against a panel of 60 human cancer cell lines.
Translesion DNA synthesis (TLS) performed by human polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived N-aryl-substituted indole barbituric acid (IBA), thiobarbituric (ITBA), and quinuclidine scaffolds identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an ITBA derivative that inhibited activity with IC50 value 8...
Glioblastoma (GBM) is highly resistant to treatment and invasion into the surrounding brain a cancer hallmark that leads recurrence despite surgical resection. With emergence of precision medicine, patient-derived 3D systems are considered potentially robust GBM preclinical models. In this study, we screened library 22 anti-invasive compounds (i.e., NF-kB, GSK-3-B, COX-2, tubulin inhibitors) using glioblastoma U-251 MG cell spheroids. We evaluated toxicity inhibition Matrigel assay. next...
A series of novel hybrid 8-hydroxyquinoline-indole derivatives (
Breast cancer progression is associated with systemic effects, including functional limitations and sarcopenia without the appearance of overt cachexia. Autocrine/paracrine actions cytokines/chemokines produced by cells mediate limitations. The cytokine-inducible transcription factor NF-κB could be central to this process, as it displays oncogenic functions integral Pax7:MyoD:Pgc-1β:miR-486 myogenesis axis. We tested possibility using MMTV-PyMT transgenic mammary tumor model inhibitor...
Overexpression of human DNA polymerase kappa (hpol κ) in glioblastoma is associated with shorter survival time and resistance to the alkylating agent temozolomide (TMZ), making it an attractive target for development small-molecule inhibitors. We previously reported on characterization indole barbituric acid-derived (IBA) inhibitors translesion synthesis polymerases (TLS pols). have now identified a potent selective inhibitor hpol κ based indole-aminoguanidine (IAG) chemical scaffold. The...
Age-progressive neurodegenerative pathologies, including Alzheimer's disease (AD), are distinguished and diagnosed by disease-specific components of intra- or extra-cellular aggregates. Increasing evidence suggests that neuroinflammation promotes protein aggregation, is involved in the etiology neurological diseases. We synthesized tested analogs naturally occurring tubulin-binding compound, combretastatin A-4. One such analog, PNR502, markedly reduced quantity Alzheimer-associated amyloid...
The cannabinoid (CB) receptors (CB1R and CB2R) represent a promising therapeutic target for several indications such as nociception obesity. ligands with nonselectivity can be traced to the high similarity in binding sites of both receptors. Therefore, need selectivity, potency, G-protein coupling bias has further complicated design desired compounds. currently studied agonists is seldom investigated, that do exhibit are typically nonselective. However, certain long-chain endocannabinoids...