Don L. Warner
Boise State University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Don L. Warner.
Cardiovascular Toxicology | 2005
Andrew M. Slupe; Berea Williams; Corianton Larson; Laura M. Lee; Toby Primbs; Amanda J. Bruesch; Chad Bjorklund; Don L. Warner; Jeffrey M. Peloquin; Susan E. Shadle; Hervé Gambliel; Barry J. Cusack; Richard D. Olson; Henry A. Charlier
Carbonyl reductase (CR) catalyzes the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of several carbonyls. Anthracyclines used to treat cancer are reduced by CR at the C13 carbonyl and the resulting metabolites are implicated in the cardiotoxicity associated with anthracycline therapy. CR also is believed to have a role in detoxifying quinones, raising the question whether CR catalyzes reduction of anthracycline quinones. Steadystate kinetic studies were done with several anthraquinone-containing compounds, including 13-deoxydoxorubicin and daunorubicinol, which lack the C13 carbonyl, thus unmasking the anthraquinone for study. kcat and kcat/Km values for 13-deoxydoxorubicin and daunorubicinol were nearly identical, indicating that that the efficiency of quinone reduction was unaffected by the differences at the C13 position. kcat and kcat/Km values were much smaller for the analogs than for the parent compounds, suggesting that the C13 carbonyl is preferred as a substrate over the quinone. CR also reduced structurally related quinone molecules with less favorable catalytic efficiency. Modeling studies with doxorubicin and carbonyl reductase revealed that methionine 234 sterically hinder the rings adjacent to the quinone, thus accounting for the lower catalytic efficiency. Reduction of the anthraquinones may further define the role of CR in anthracycline metabolism and may influence anthracycline cytotoxic and cardiotoxic mechanisms.
Bioorganic & Medicinal Chemistry | 2010
Solomon Berhe; Andrew M. Slupe; Choice Luster; Henry A. Charlier; Don L. Warner; Leon H. Zalkow; Edward M. Burgess; Nkechi M. Enwerem; Oladapo Bakare
A series of indazole-dione derivatives were synthesized by the 1,3-dipolar cycloaddition reaction of appropriate substituted benzoquinones or naphthoquinones and N-carboalkoxyamino diazopropane derivatives. These compounds were evaluated for their effects on human carbonyl reductase. Several of the analogs were found to serve as substrates for carbonyl reductase with a wide range of catalytic efficiencies, while four analogs display inhibitory activities with IC(50) values ranging from 3-5 microM. Two of the inhibitors were studied in greater detail and were found to be noncompetitive inhibitors against both NADPH and menadione with K(I) values ranging between 2 and 11 microM. Computational studies suggest that conformation of the compounds may determine whether the indazole-diones bind productively to yield product or nonproductively to inhibit the enzyme.
Bioorganic & Medicinal Chemistry | 2015
Chris Mallory; Ryan Carfi; SangPhil Moon; Kenneth A. Cornell; Don L. Warner
Two synthetic aziridinomitosenes (AZMs), Me-AZM and H-AZM, structurally related to mitomycin C (MC) were evaluated for their anticancer activity against six cancer cell lines (HeLa, Jurkat, T47D, HepG2, HL-60, and HuT-78) and tested for their DNA-modifying abilities in Jurkat cells. Cytotoxicity assays showed that Me-AZM is up to 72-fold and 520-fold more potent than MC and H-AZM, respectively. Me-AZM also demonstrated increased DNA modification over MC and H-AZM in alkaline COMET and Hoechst fluorescence assays that measured crosslinks in cellular DNA. Me-AZM and H-AZM treatment of Jurkat cells was found to sponsor significant DNA-protein crosslinks using a K-SDS assay. The results clearly indicate that the AZM C6/C7 substitution pattern plays an important role in drug activity and supports both DNA-DNA and DNA-protein adduct formation as mechanisms for inducing cytotoxic effects.
Journal of Chemical Education | 2013
Aubrey Johnston; Jonathan Scaggs; Chris Mallory; Andrea Haskett; Don L. Warner; Eric C. Brown; Karen Hammond; Michael M. McCormick; Owen M. McDougal
Journal of Chemical Education | 2012
Clifford M. Csizmar; Dee Ann Force; Don L. Warner
Journal of STEM Education: Innovations and Research | 2015
Louis S. Nadelson; Don L. Warner; Eric C. Brown
Journal of Chemical Education | 2011
Nicholas A. Weires; Aubrey Johnston; Don L. Warner; Michael M. McCormick; Karen Hammond; Owen M. McDougal
Journal of Chemical Education | 2013
Clifford M. Csizmar; Jeremy P. Daniels; Lauren E. Davis; Tyler P. Hoovis; Karen Hammond; Owen M. McDougal; Don L. Warner
Journal of Chemical Education | 2012
Susan E. Shadle; Eric C. Brown; Marcy H. Towns; Don L. Warner
Journal of Chemical Education | 2011
Clifford M. Csizmar; Dee Ann Force; Don L. Warner