In the tropical rain forests of Sarawak on the island of Borneo grows afair-size tree that scientists at the National Cancer Institute (NCI) say"may have advantageous pharmacologic, toxicologic and/or anti-viralproperties, especially in the treatment of AIDS."The chief of NCI's Natural Products Branch, Gordon Cragg, toldBioWorld that the tree's novel class of anti-HIV compounds, thecalanolides, "strongly inhibit HIV-1 replication in vitro."Cragg co-authored the only report on the subject two years ago in theAmerican Chemical Society's Journal of Medicinal Chemistry (1992:V. 35, No. 15), titled "The Calanolides, a Novel HIV-Inhibitory Classof Coumarin Derivatives From the Tropical Rain Forest Tree,Calophyllum lanigerum."Coumarin, (C9H6O2), is a secondary plant metabolite currently usedmedically as a blood coagulant, and industrially in perfumes and todisguise unpleasant odors.Calanolides extracted from the tree's twigs and fruit, the journal paperreported, "were completely protective against HIV-1 replication andcytopathicity ...but were inactive against HIV-2." Moreover, one of thecompound's chemical variants, calanolide A, "was active not onlyagainst the AZT-resistant strain of the virus, but also against thepyridinone strain." It acts specifically against HIV-1 reversetranscription.Sarawak is an offshore annex of Malaysia. NCI is now extensivelysurveying its flora to assess the distribution of the Calophyllumlanigerum tree. This exploration has already turned up a second,related, species, Calophyllum teysmannii, which yields a differentsecondary metabolite, costatolide. This has the same in vitro propertiesas the calanolide. But, said Cragg, "it has one particularly attractivefeature; its latex can be tapped for the compound, rather than strippingthe tree of leaves and twigs. That makes it a renewable resource."License Applicants Must Deal With SarawakOn March 30, the Federal Register carried a notice inviting bids fromcompanies interested in developing, clinically testing and bringing tomarket future anti-AIDS drugs protected by NIH's two pending patentapplications, both headed, "Calanolide Antiviral Compounds,Compositions and Uses Thereof.""In view of the high priority for developing new drugs for thetreatment of HIV infection," reads the notice, "all [licensing] proposalsmust be received 60 days from the date of this publication" - by May29."As the U.S. is sensitive to biodiversity policies of other countries,"Steven Ferguson, the NIH's licensing specialist, told BioWorld, andsince "the calanolide compounds are isolated from flora indigenous toSarawak," the licensee selected to "pursue the preclinical, clinical andcommercial development of these compounds" must do so inagreements negotiated "with the appropriate Sarawak governmentagencies."To contact Ferguson, call the NIH Office of Technology Transfer:(301) 496-7735; Fax: (301) 402-0220.Requests for technical data on calanolide's anti-HIV activity should beaddressed to Dr. Dwight Kaufman, deputy director of NCI's Divisionof Cancer Treatment. Telephone: (301) 496-6711.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.