Natural Antiepileptic Inhibitors and New Molecular Treatments for Diabetes

By virtue of structural diversity and novelty, natural products offer exciting opportunities for drug discovery and development. During the last several years, our research group is actively involved in the discovery of bioactive natural products, isolated from medicinal plants, marine organisms, and microorganisms.

Epilepsy is among the leading neurological disorders in the world. Antiepileptic medicines currently used in clinical practices suffered from several problems. The prolong use of synthetic epileptic drugs cause neurotoxicity and other side effects. Additionally nearly all currently used medicines only manage the symptoms and do not treat the disease. Thus the ultimate goal is to develop ideal antiepileptic agents those that are safe, specific, effective, orally bioavailable and address the underlying problem. Based on this need, we screened a large number of medicinal plants used for the treatment of epilepsy in folk medicines. As a result of this long and systematic search, two potent antiepileptic constituents, isoxylitones A and B, along with their precursors, were isolated from Delphenium denudatum and Aconitum lavae.

These studies have resulted in the identification of several classes of novel pharmacophores, which were then used to build libraries of analogues to study their structure-activity relationship. During this presentation, the underlying philosophy and results of these studies will be presented.

Diabetes is an old disease that poses a new challenge to human well being. It is characterized by hyperglycemia and associated complications. It is the third major cause of death, after cancers and heart diseases. In many parts of the world, diabetes has taken the shape of an epidemic, and various un-conventional forms of diabetes have been recently been discovered. It is predicted that by the year 2010, diabetic patients will number over 220 million, posing a major challenge to the healthcare and social welfare systems.

Current treatments of diabetes are based on reducing insulin resistance, increasing endogenous insulin production, exogenous insulin supplies, reducing hepatic glucose production, and limiting the postprandial glucose absorption. Among different therapeutic interventions, the discovery of effective α-glucosidase inhibitors and antiglycating agents are considered to be the most important one, based on modern knowledge about the disease at molecular level.

The primary focus of these studies has been to discover lead bioactive molecules by using appropriate conventional and mechanism-based biological screening techniques. As a result, a large number of potent antiglycation agents of natural origin were discovered and structure-activity relationship studies were conducted. Many of these compounds represent new examples of inhibitors α-glucosidase and glycation.