A study of redox, and other relevant physical properties of a new class of nitroaromatic compounds, i.e., the benzazolo[3,2-a]quinolinium salt derivatives (QSDs), will be performed in order to understand the cytotoxic mechanisms of these compounds. Due to the presence of nitrosubstituents in these compounds and their affinity for DNA, the possibility of a preferred reactivity of these compounds toward DNA and proteins under anoxia will be examined since this could lead to a new series of compounds which could serve as hypoxia-specific cytotoxins or antitumor agents. For this purpose, possible DNA damaging and protein thiol consumption reactions by QSDs will be tested in the absence and presence of air and in the absence and presence reducing agents. Correlations will be sought between the QSDs reactivities detected in this work and anoxic or aerobic cytotoxicities. These reactivities will be compared to those of well known hypoxic-specific toxic compounds.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15CA082142-01
Application #
2881337
Study Section
Chemical Pathology Study Section (CPA)
Program Officer
Grotzinger, Karen R
Project Start
1999-09-01
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2002-08-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Puerto Rico at Humacao
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Humacao
State
PR
Country
United States
Zip Code
00791
Roginsky, Vitaly; Alegria, Antonio E (2005) Oxidation of tea extracts and tea catechins by molecular oxygen. J Agric Food Chem 53:4529-35
Alegria, Antonio E; Sanchez-Cruz, Pedro; Rivas, Lilyvet (2004) Alkaline-earth cations enhance ortho-quinone-catalyzed ascorbate oxidation. Free Radic Biol Med 37:1631-9
Alegria, Antonio E; Sanchez, Sheila; Quintana, Ingrid (2004) Quinone-enhanced ascorbate reduction of nitric oxide: role of quinone redox potential. Free Radic Res 38:1107-12
Alegria, Antonio E; Flores, Wilmarie; Cordones, Emelyn et al. (2004) Reductive activation and thiol reactivity of benzazolo[3,2-a]quinolinium salts. Toxicology 199:87-96