This proposal requests funds to permit Dr. Wayne T. Shier, Professor, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Minnesota, to pursue with Dr. William G. Padolina, Director, National Institutes of Biotechnology and Applied Microbiology, University of the Philippines, Los Ba~os, for a period of 24 months, a program of cooperative research on cytotoxic and antiviral agents from natural sources in the Philippines. A minimal mammalian cell culture capability will be established in the Philippines. It will be used to conduct cytotoxicity assays against normal and transformed permanent cell lines and antiviral assays against a DNA virus (Herpes simplex type 1) and an RNA virus in ethanol extracts from Philippine medicinal plants with emphasis on plants known to be toxic or to contain anti-fertility or insecticidal activities. A second source of extracts will be marine plants and lower animals, with particular emphasis on sponges and tunicates. A third source of extracts will be toxic fungi from agricultural extension samples received from all parts of the Philippines. Extraction, purification, and structure identification efforts will be carried out on any specimen found to have noteworthy cytotoxic or antiviral activities. Some 200 medicinal plants, marine organisms, and fungal isolates will be screened for cytotoxic and antiviral agents. The researchers will attempt to gain some insight into the roles of toxins in the organisms that produce them. The search for antiviral agents is presently one of the most active areas of research in the pharmaceutical sciences. Efforts in this area have been spurred on by (1) the lack of effective agents for viral chemotherapy in general, and in particular from widespread public concern about AIDS and (2) recent successes with synthetic analogs of marine natural products. The search for anti-cancer (cytotoxic) agents has met with some successes in extracts from marine plants and lower animals from the Caribbean. The proposed research will extend these lines of investigation to the vast and largely untapped resource of biological and biochemical diversity provided by the marine and terrestrial environments of the Philippines. This project is relevant to the objectives of the Science in Developing Countries Program which seeks to increase the level of cooperation between U.S. scientists and engineers and their counterparts in developing countries through the exchange of scientific information, ideas, skills, and techniques and through collaboration on problems of mutual benefit. In addition, the project will improve Philippine scientific infrastructure through the establishment of a mammalian cell culture capability at Los Ba~os. The U.S. and Philippine collaborators are highly respected scientists with extensive research experience and productive publication records in the field of the proposal.
