. Natural products research during the last few decades has yielded thousands of novel organisms from the marine environment. The bioassays guiding these isolations typically have been based on antimicrobial, antitumor, antiviral, or antiinflammatory actvities. Little has been done to explore the oceans for compounds with activity against HIV and AIDS OI. Additionally, because of the limits associated with the conventional Self-Contained Underwater Breathing Apparatus (SCUBA), the majority of the compounds characterized from the marine environment are the results of shallow-water collections (-30 meters). The value of mass screening of complex extracts of natural products coupled with bioactivity-guided fractionation and compound identification for the discovery of new natural product chemotypes is well known. The primary focus of this application is on the isolation and characterization of new chemotypes for the potential treatment of AIDS and AIDS-related opportunistic infections (OI), and the applicant will collect and screen marine samples in relevant bioassays. Samples will be obtained from depths of 0 to -800 meters, and among the collection methods used will be CCUBA (Closed Circuit Underwater Breathing Apparatus), which will permit longer and deeper dives than possible by SCUBA, and will allow the applicant to work on previously unexplored marine benthic species. Active extracts of organisms will be isolated using various chromatographic techniques inclusive of HPLC, and chemical structures of biologically active secondary metabolites will be determined through spectroscopic and chemical methods, with special emphasis on two- dimensional NMR techniques. Additional quantities of particularly promising compounds that are required for in vivo testing will be obtained via synthesis, semi-synthesis, or repeated isolation.
