Soon, New Pills to Treat Neurological Diseases

A promising step on the road to developing new drugs for a variety of neurological diseases has been made by University of Notre Dame researchers.

A promising step on the road to developing new drugs for a variety of neurological diseases has been made by University of Notre Dame researchers. They were able to take this step by focusing on the design, synthesis and evaluation of water-soluble "gelatinase inhibitor" compounds.

Gelatinases, a class of enzymes, have been implicated in a host of human diseases from cancer to cardiovascular conditions and in particular neurological conditions such as stroke, aneurysm and traumatic brain injury.

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The Notre Dame group has been investigating variants of a compound called "SB-3CT," which shows promise as a selective and potent gelatinase inhibitor.

The preferred method of treatment for acute gelatinase-dependent diseases is intravenous infusion. Intravenous administration requires that the compound be water-soluble.

Unfortunately SB-3CT has poor water solubility and poor drug-like properties.

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In a new approach, the group from the University's Departments of Chemistry and Biochemistry and Biological Sciences and the Friemann Life Sciences Centre, used a prodrug strategy to address this issue.

A prodrug is an inactive precursor of a drug that is converted into its active form in the body by normal metabolic processes.

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The prodrug strategy produced a greater than 5,000-fold increase in water solubility compared to SB-3CT.

In addition to its high water solubility, the prodrug (referred to as ND-478) was chemically stable, non-toxic and was quickly converted to the active drug in the blood.

These favourable properties of ND-478 make it suitable for intravenous administration in the treatment of acute gelatinase-dependent diseases.

Such a compound offers the possibility of translation into the clinic for treatment of strokes, aneurysms and traumatic brain injury.

Source-ANI