Grant: Discovery Grants Program - Individual

Bioprospecting of plants, based on ethnomedical knowledge, holds out the possibility for discovering new pharmaceuticals. For instance, combretastatins are a group of anti-mitotic agents isolated from the bark of the South African tree, Combretum caffrum. Paclitaxel (Taxol?), an anti-cancer drug, was isolated from the Pacific yew tree, Taxus brevifolia. Enzymes play a significant role in performing various biochemical processes including metabolism, catabolism, cellular signal transduction, cell cycling and development. Any malfunction in these biochemical processes leads to diseases and discomforts. Malfunctioning of biochemical processes is due to the dysfunction of enzymes as well as overexpression or hyperactivation of enzymes. These malfunctions may be corrected by using appropriate enzyme inhibitors. Based on the importance of enzyme inhibitors in human's life, we are interested in discovering acetylcholinesterase, alpha-glucosidase and glutathione S-transferase inhibitors from medicinally important plants. Natural products with these biological activities might have applications in curing Alzhemier's disease, diabetic or improvements of anti-cancer/anti-parasitic chemotherapy. We have collected a number of plants including Artemisia absinthium, Solidogo rigida, Sorbus scopulina, Ribes americanum, Lilium tomentosa, Drypetes natalensis, Combretum bracteosum, Vepris lanceolata, and Anastrabe integerima etc. from Manitoba and South Africa. All of these plant extracts exhibited enzyme inhibitory and antimicrobial activities in our bench top bioassays. The major objectives of the proposed research are: (i) bioassay-guided isolation of bioactive natural products from medicinally important plants (ii) structure determination of bioactive compounds with the aid NMR and mass spectroscopic methods (iii) structural modifications of bioactive natural products using chemical and microbial reactions to study their structure-activity relationships (iv) detailed in-vitro and in-vivo study of bioactivity of potent bioactive compounds.