This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Microwave assisted organic synthesis (MAOS) is being employed to synthesize cytotoxic arylphosphonium salts (APS). APS exhibit structure-activity relationships as antibiotics, in DNA binding, enzyme inhibition and against malignant cells. They cross cell membranes and accumulate in mitochondria of malignant cells. They deliver DNA alkylating agents into cancer cells, inhibit acetylcholinesterase, bovine serum amine oxidase, protein kinase C and HIV integrase. Among possible consequences are disruption of metabolism and cell division from blocked enzymes and interference with replication. A report of the latter with student co-authors has been published. APS effects in DNA melting, electrophoresis, and isothermal titration calorimetry are being studied. A student co-authored article on in silico APS-estrogen-receptor binding has been published. We will do further experiments at RIC and Brown EPSCoR on toxicity mechanisms of APS. We have synthesized new APS-fluorescent conjugates and observed their uptake by live cells. We have prepared APS polymers and graft polymers that are antibiotic. AutoDock, HyperChem and eHitsLightning will and are being used to calculate APS-DNA interactions. Polymeric APS will be tested further for antibacterial activity for potential use in medical plastics. New APS will be screened for DNA-replication toxicity. A crystallization project to make complexes for X-ray structure determination is underway and crystals have been isolated from DNA-APS hanging-drop experiments. Solid-state polypeptide synthesis will provide polypeptides for conjugates to APS and for DNA complexing studies. Triphenyltriazoles will be synthesized and incorporated into polypeptide co-polymers to make antibiotic and/or biodegradable macromolecules.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016457-11
Application #
8360079
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
11
Fiscal Year
2011
Total Cost
$10,749
Indirect Cost
Name
University of Rhode Island
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
144017188
City
Kingston
State
RI
Country
United States
Zip Code
02881
Hahn, Mark E; Karchner, Sibel I; Merson, Rebeka R (2017) Diversity as Opportunity: Insights from 600 Million Years of AHR Evolution. Curr Opin Toxicol 2:58-71
Preiss, Matthew R; Cournoyer, Eily; Paquin, Karissa L et al. (2017) Tuning the Multifunctionality of Iron Oxide Nanoparticles Using Self-Assembled Mixed Lipid Layers. Bioconjug Chem 28:2729-2736
Taylor, David L; Williamson, Patrick R (2017) Mercury contamination in Southern New England coastal fisheries and dietary habits of recreational anglers and their families: Implications to human health and issuance of consumption advisories. Mar Pollut Bull 114:144-156
Tiwari, Rakesh K; Brown, Alex; Sadeghiani, Neda et al. (2017) Design, Synthesis, and Evaluation of Dasatinib-Amino Acid and Dasatinib-Fatty Acid Conjugates as Protein Tyrosine Kinase Inhibitors. ChemMedChem 12:86-99
Wan, Jerry; Lin, Fuquan; Zhang, Wei et al. (2017) Novel approaches to vitiligo treatment via modulation of mTOR and NF-?B pathways in human skin melanocytes. Int J Biol Sci 13:391-400
Malloy, Thomas E; Kinney, Lorin (2017) Implications for the Self Determine Benevolence and Self-Protection in Intergroup Relations. Self Identity 16:171-193
Vierra, David A; Garzon, Jada L; Rego, Meghan A et al. (2017) Modulation of the Fanconi anemia pathway via chemically induced changes in chromatin structure. Oncotarget 8:76443-76457
Zhang, Jiyong; Klufas, Daniel; Manalo, Karina et al. (2016) HMGB1 Translocation After Ischemia in the Ovine Fetal Brain. J Neuropathol Exp Neurol 75:527-38
Donepudi, Ajay C; Cheng, Qiuqiong; Lu, Zhenqiang James et al. (2016) Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression. Drug Metab Dispos 44:518-26
Ma, Hang; Liu, Weixi; Frost, Leslie et al. (2016) Glucitol-core containing gallotannins inhibit the formation of advanced glycation end-products mediated by their antioxidant potential. Food Funct 7:2213-22

Showing the most recent 10 out of 370 publications