U.S.-Philippines Cooperative Research on Cytotoxic and Anti-viral Agents in Philippine Plant and Animal Species

本提案要求资金允许明尼苏达大学药学院药物化学和生药学系教授Wayne T. Shier博士与菲律宾大学Los Ba~os国家生物技术和应用微生物研究所所长William G. Padolina博士进行为期24个月的研究。菲律宾一项关于天然来源的细胞毒性和抗病毒药物的合作研究方案。将在菲律宾建立最低限度的哺乳动物细胞培养能力。它将用于对正常和转化的永久细胞系进行细胞毒性试验，并对菲律宾药用植物乙醇提取物中的DNA病毒（1型单纯疱疹病毒）和RNA病毒进行抗病毒试验，重点是已知有毒或含有抗生育或杀虫活性的植物。萃取物的第二个来源将是海洋植物和低等动物，特别强调海绵和被囊动物。萃取物的第三个来源将是来自菲律宾各地农业推广样本的有毒真菌。提取、纯化和结构鉴定工作将对任何发现具有显著细胞毒性或抗病毒活性的标本进行。大约200种药用植物、海洋生物和真菌分离物将被筛选为细胞毒性和抗病毒药物。研究人员将试图深入了解毒素在产生毒素的生物体中的作用。寻找抗病毒药物是目前制药科学研究中最活跃的领域之一。这一领域的努力受到以下因素的推动：(1)普遍缺乏有效的病毒化疗药物，特别是公众对艾滋病的广泛关注；(2)最近海洋天然产物合成类似物的成功。在加勒比海的海洋植物和低等动物的提取物中，对抗癌（细胞毒性）制剂的研究取得了一些成功。拟议的研究将把这些调查范围扩展到菲律宾海洋和陆地环境提供的大量尚未开发的生物和生化多样性资源。该项目与“发展中国家科学项目”的目标相关，该项目旨在通过科学信息、思想、技能和技术的交流以及在互利问题上的合作，提高美国科学家和工程师与发展中国家同行之间的合作水平。此外，该项目将通过在Los Ba~os建立哺乳动物细胞培养能力来改善菲律宾的科学基础设施。美国和菲律宾的合作者是备受尊敬的科学家，在提案领域拥有丰富的研究经验和富有成效的出版记录。

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.