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Calanolide A is a novel coumarin isolated from the leaves and twigs of a tree collected in the 

 rainforest regions of Sarawak, Malaysia. Calanolide A shows potent in vitro activity against 

 HIV-1 and several resistant strains of the virus, but not against HIV-2, and is in early 

 preclinical development. Recollections of plant material of the original plant species from the 

 same general location have shown a range of test results varying from reasonable activity to 

 total lack of activity. It is apparent that the production of calanolide A is dependent on 

 various factors, possibly including the immediate growth environment and the time of 

 harvest. Thus far, calanolide A has not been detected in any of the recollections, and the 

 original source tree cannot be located. Careful taxonomic and chemotaxonomic studies of 

 this species are being performed by the UIC, under contract to and in collaboration with the 

 NCI and scientists from Sarawak. A survey of related species has shown that the latex of 

 another species collected in the same region yields the related compound, costatolide, which 

 has significant in vitro anti-HTV activity, though being somewhat less active than calanolide 

 A. Costatolide and a derivative have also been approved for preclinical development. The 

 latex contains high yields of costatolide, and would be an excellent renewable source of the 

 compound, should it advance to clinical development. In addition, the synthesis of calanolide 

 A has recently been reported. 



A novel chemical compound, conocurvone, has been isolated from a plant species endemic to 

 Western Australia; this plant was originally collected for the NCI program by the USDA in 

 1981. Conocurvone exhibits potent in vitro activity against HIV-1 and is in early preclinical 

 development. Conocurvone has been synthesized from a simpler chemical which can also be 

 isolated from the plant, and in addition, other simpler analogs have been synthesized and 

 shown to possess equivalent in vitro anti-HIV activity. The development of conocurvone or 

 related compounds will be undertaken in close collaboration with Australian scientists, and 

 surveys of the occurrence and abundance of the source plant and related species are being 

 carried out by the Western Australian Department of Conservation and Land Management. 



Another potential anti-HIV agent, prostratin, has been isolated from the stemwood of a 

 Western Samoan tree. This tree is used in Western Samoa for the treatment of a variety of 

 diseases, including yellow fever, and an extract of the stemwood was provided by Dr. Paul 

 Cox of Brigham Young University. While prostratin belongs to the phorbol class of 

 compounds which frequently exhibit significant tumor promoting properties, it does not 

 appear to be associated with tumor promotion, and has been selected for early preclinical 

 development. 



Of the approximately 30,000 extracts tested so far in the in vitro human cancer cell line 

 screen, which started after the anti-HIV screen, a very small percentage (< 1.0 percent) have 

 shown some degree of selective cytotoxicity. Interesting, novel patterns of differential 

 cytotoxicity have been observed, and while some have been associated with known classes of 

 compounds, others appear to be new leads which are being investigated further. Two natural 

 products currently approved for preclinical development are halomon, isolated from a red 

 algae collected in the Philippines, and halichondrin B, isolated from a species of marine 



