New chemistry being developed for delivery of neuroprotec...( Update: Emre Isin received the second...),Health

(Blacksburg, Va.) -- One approach to treating neurodegenerative disease such as Parkinson's disease is to interfere with the chemistry involved. Thus, scientists study the brain's chemical pathways and try to identify potential roadblocks.

At the 222nd national meeting of the American Chemical Society Aug. 26-30 in Chicago, Virginia Tech researchers will present their advancements in the development of such roadblocks.

Monoamine oxidases (MAO) A and B and the neuronal form of nitric oxide synthase (nNOS) are two enzyme systems thought to be involved in neurodegenerative pathways in Parkinson's disease. A synthetic compound which inhibits both enzymes, 7-nitroindazole, has been shown to have neuroprotective effects in animal models. However, experimentation was curtailed because of the compound's limited solubility.

Now, Virginia Tech researchers are developing a "prodrug" that will be a water soluble form of the parent compound and will be activated in the body to release the parent compound, explains Emre M. Isin.

Isin, who is from Istanbul, Turkey, is a Ph.D. student working in the Department of Chemistrys Harvey W. Peters Center at Virginia Tech. He explains that he and Neal Castagnoli, center director, have attached a "sidecar" to the parent compound that makes the entire drug water soluble and will facilitate its administration and distribution throughout the body. The sidecar a tetrahydropyridinyl moiety -- is a nontoxic carrier that detaches from the parent compound following interaction with MAO.

The use of tetrahydropyridinyl moiety to prepare a soluble prodrug of a certain molecule is a powerful approach to drug design. So far, experiments have only been done in the lab (in vitro). Isin explains, "Inhibitors of the two enzymes, MAO and nNOS
'"/>

Contact: Emre Isin
eisin@vt.edu
540-231-8233
Virginia Tech
28-Aug-2001