Spotlight on Research: Davies Looks for Ways to Deliver Nitric Oxide for Medical Uses
Posted: April 3, 2003 at 1:00 am, Last Updated: November 30, -0001 at 12:00 am
By Lynn Burke
Nitric oxide was once considered only a pollutant, something found in acid rain and smog. About 15 years ago, however, people recognized that various bioregulatory functions were associated with the compound, says Keith Davies, professor of chemistry at George Mason. That discovery has led to an increase in biomedical research on the compound, and Davies’s work has contributed to the field. This June, he will finish up a three-year grant from the National Institutes of Health (NIH) on the Biomimetic Study of Nitric Oxide Donor Compounds.
Nitric oxide has been found to play a role in blood pressure regulation, blood clotting, neurotransmission, and penile erection, says Davies. The finding has created the need for compounds that can conveniently generate nitric oxide for use in laboratory studies and as potential drugs that can deliver the compound to diverse biological sites. Diazeniumdiolates, a class of compounds developed by a group at the National Cancer Institute (NCI) led by Larry Keefer, have been found to be one of the best compounds for generating nitric oxide in solution, says Davies.
Davies, who worked on nitric oxide reactions with metals while completing his Ph.D., began collaborating with Keefer about eight years ago. At the time, Davies was interested in becoming involved in this new area of nitric oxide research, and Keefer was looking for someone who could work on rate and mechanistic studies of the reactions in which they were interested.
Based on the work he had done with Keefer and his group, Davies applied for and received an NIH grant to do work at George Mason on the factors that influence the rates of nitric oxide release from diazeniumdiolates under conditions that mimic the conditions the compounds would likely encounter in the body. Data obtained from the project may help in physically targeting diazeniumdiolates, he says, which would avoid distributing the compound throughout the body and exposing sensitive parts to nitric oxide’s multipotent effects.
One outcome of the research has been some excellent work on the part of students. Davies notes in particular Stacy Price, a chemistry graduate student who presented a poster on the diazeniumdiolate research at the 2002 national meeting of the American Chemical Society and another at the 2003 national meeting in New Orleans last month. She plans to pursue a degree in patent law at George Mason’s Law School after she obtains her M.S. degree this summer. Other Mason students working with Davies who contributed to the papers were Dilara Jappar, who is currently in the pharmacy Ph.D. program at the University of Maryland; David Byer, who has been accepted into the M.D. program at the University of Miami; and Patricia Lorenzo, who is to attend pharmacy school.
Davies, who continues his collaborative work with Keefer’s team at NCI, says that the work in the field is still preliminary and most clinical applications are a ways off. He notes, however, that one class of diazeniumdiolate compound shows promise for the treatment of acute myeloid leukemia, and another, in aerosolized form, has been administered to a human patient with acute respiratory distress syndrome.