More MS news articles for Sep 2001

New chemistry being developed for delivery of neuroprotective drugs

Contact: Emre Isin
Virginia Tech

(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 Chemistry’s 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, have been studied separately by different groups. Our work focuses on demonstrating that the prodrug will be bioactivated by MAO to yield products that will activate neuroprotective mechanisms. We are also testing other derivatives to get a better understanding of the active site in the MAO enzyme."

Isin will deliver his poster, "Studies on the synthesis and biological evaluation of potential tetrahydropyridinyl prodrugs of indazolyl derivatives as neuroprotective agents (TOXI 48)" on Tuesday, Aug. 28 at 5:30 p.m. in the Hyatt Regency Chicago Regency rooms A-B