Novel bioactive compounds from endophytic fungi of Aborininal medicinla plants

Abstract

Natural products exhibit interesting anti-microbial, anti-viral, and anti-inflammatory activities. These bioactivities make them an important source for the discovery of new pharmaceuticals. Currently, more than 60% of the drugs available on the market are of natural product origin. One of the aspects of drug discovery process is the identification of small molecules with enzyme-inhibiting activities. Enzymes are essential to human life, mediating biochemical processes including metabolism, cellular signal transduction, cell cycling, and development. Malfunction in these biochemical systems often leads to disease that can be caused either by the dysfunction, overexpression, or hyper-activation of the enzymes involved. An understanding of diseases at the molecular level has provided several enzyme inhibitors in clinics. For instance, galanthamine, a potent acetylcholinesterase (AChE) inhibitor, is used to treat early symptoms of Alzheimer's disease. α-Glucosidase (EC 3.2.1.20) is a membrane bound enzyme and lies at intestinal cells. This enzyme catalyzes the final step of carbohydrates digestion by hydrolyzing the glycosidic bonds in carbohydrates to liberate free glucose. The resulting glucose is a source of an exaggerated rise in blood sugar causing postprandial hyperglycemia. This causes type 2 diabetes mellitus and affects approximately 2.1 billion people worldwide. The potent α-glucosidase inhibitors prevent the breakdown of carbohydrates in small intestine and prolong the absorption of glucose or carbohydrates in blood. These compounds may be used as chemotherapeutic agents in clinics for the treatment of diabetes and obesity. Due to the catalytic role of α-glucosidase in carbohydrate digestion, these inhibitors may also be used as therapeutic target for other carbohydrate mediated diseases including viral infections, cancer, HIV and hepatitis. Our recent chemical investigation of endophytes of Aboriginal medicinal plants of Canada resulted in the identification of natural products exhibiting potent bioactivities including anti-microbial, anti-α-glucosidase and anti-AChE activities. In this presentation, isolation, structure elucidation of new bioactive natural products and their structure-activity relationships will be discussed.