Novel enzyme inhibiting natural products from medicinally important plants

Abstract

Natural products derived from plants, marine organisms and microorganisms exhibit interesting anti-microbial, anti-viral, and anti-inflammatory activities. These bioactivities make natural products an important source for the discovery of new pharmaceutical agents, and 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 Alzheimer's disease. In-vitro enzyme inhibition assays can easily be performed in any natural product chemistry lab in order to discover lead compounds against various biological targets. For instance, glutathione S-transferase (GST) inhibitors have applications in overcoming the drug resistance problems in cancer and parasite chemotherapy. Fatty acid synthase inhibitors are used to discover anti-malarial, anti-parasitic, anti-TB and anti-fungal compounds. We are involved in discovering new enzyme inhibitors from medicinally important plants. These efforts have resulted in the identification of a few novel AChE, GST and α-glucosidase inhibitors. During this presentation, structure elucidation of these new enzyme inhibitors and their bioactivity data will be discussed. Additionally, results obtained from structure-activity relationship studies will also be presented.