The goals of this AP are 1) to identify and characterize the biologically active constituents of plants used as remedies in African ethnomedicine; 2) to carry out the optimization of selected lead compounds with potential for human health in Africa; and 3) to train a cadre of young African scientists in natural products chemistry and synthetic medicinal chemistry. We will conduct the extraction of selected medicinal plants, perform initial bioassay screens of extracts and conduct bulk extraction of plant material for drug development. An inventory of the extracts, their distribution and their status in the test systems will be maintained. Sufficiently active extracts will undergo bioassay-guided fractionation. We will use three bioassays: the brine shrimp lethality bioassay, a rapid, low-cost test for biologically active compounds, a potato disc assay for antiviral and cytotoxic properties, and an antimicrobial test using a panel of fungi as well as gram-positive and gram-negative bacteria. In addition, we will test extracts for potential agricultural protection properties. The active compounds will be isolated by a combination of chromatographic techniques. The structure of isolated compounds will be determined by a combination of spectra studies and chemical analyses, and the structure-activity relationship will be determined for the isolated chemical class. A lead optimization program based on isolated compounds from selected plants will be undertaken to increase their therapeutic potential as antimalarials and antileishmanials. Some extracts will be developed as phytomedicines for domestic marketing, while others will be sent to the appropriate individuals and institutions within this ICBG for further development as pharmaceuticals. We will maintain a database of phytomedical information which will be linked with the databases of ecology and ethnobotany developed by the other APs.
