. The applicant's laboratory is involved in a continuing study of medicinal plants as a source of new chemotherapeutic agents. As part of this research, the long-term objective of this proposal is the discovery of plant-derived natural products and their analogs as anti-HIV agents with novel structures and mechanisms of action. Specifically, Dr. Lee proposes to isolate and characterize the potent anti-HIV principles from extracts of 64 selected plant species which have not been investigated previously for their anti-HIV constituents. Selection of extracts for investigations will be based on a preliminary in-house demonstration of potent inhibition of HIV replication in H9 lymphocytes and/or of HIV reverse transcriptase. Bioactivity-directed fractionation and isolation of the active principles will be guided by an in vitro P24 antigen capture assay in H9 lymphocytes. The structures of the anti-HIV principles so isolated will be determined using modern physical methods, including spectral and X-ray analyses. New active leads discovered from this study will be selected for structural modifications and synthesis of analogs to determine structure-activity relationships and their mechanism of action in cell culture-based assays, as well as to improve the pharmacological profiles of the parent compounds.
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