Sooner or later the rational drug designers and protein engineers willget their atomic acts together and match up their compounds with themolecular configurations of disease entities. Meanwhile, drugdiscoverers need all the help they can get from witch doctors, shamans,nature healers and medicine men.These jungle-wise practitioners of ethnopharmacology know the fruits,twigs and roots to prescribe for the illnesses and lesions that afflicttheir peoples. For over a decade, the National Cancer Institute (NCI)has been interviewing these wise people, and collecting botanicalspecimens to screen for anti-tumor and anti-AIDS bioactivity.One such plant is Homalanthus nutans, a small tree that grows inWestern Samoa. Samoan "taulasea" (herbal healers) brew a tea from itsleaves to treat back pain and abdominal swelling; they use the roots tosuppress diarrhea, and the stem wood against yellow fever.Biochemical pharmacologist Michael Boyd, who heads the NCI'sLaboratory of Drug Discovery research and development in Frederick,Md., found that an extract of H. nutans called prostatin has "potentcytoprotective effects in human lymphocyte cells infected with thehuman immunodeficiency virus (HIV-1)."In the Aug. 8 Federal Register, NCI offered industry "exclusive or non-exclusive licenses [to] pursue the preclinical, clinical and commercialdevelopment of prostatin for the treatment of HIV infection," and itsdevelopment to "a marketable status."In collecting and using H. nutans natural plant material in Samoa, thechosen licensee or licensees must "negotiate with appropriate Samoangovernment agencies" to respect policies governing biodiversity.MediChem Tapped For Exclusive LicenseMeanwhile, NCI is about to offer an exclusive license to extracts ofanother exotic anti-AIDS plant, Calophyllum lanigerum, to MediChemResearch, Inc., a contract drug synthesis firm in Lamont, Ill. Theagency forwarded the Federal Register a notice to this effect last week.C. lanigerum grows in the tropical rain forest of Sarawak, a part ofMalaysia on the island of Borneo. The tree's fruit and twig samplesyield a novel class of compounds, the calanolides. Two of these, Boydreported, calanolides A and B, "were completely protective againstHIV-1 replication and cytopathicity"Studies with purified bacterial reverse transcriptase revealed that thecompounds inhibit HIV-1, but not HIV-2. "The calanolides," Boydwrote, "provide a novel new anti-HIV chemotype for drugdevelopment."MediChem came upon Boyd's reports of these coumarin-derivedcalanolides in the Journal of Medicinal Chemistry, and obtained aPhase I Small Business Innovative Research grant to synthesize thecompounds for NCI to test. The exclusive license proposed by NCI willbe royalty-bearing, and "probably" limited to the treatment of AIDS."We've been working with Michael Boyd because he's basically thefather of the field," medicinal chemist Michael Flavin, MediChem'spresident, told BioWorld Today. "He obviously has the biologicalexpertise to tell us whether we're on the right track."That track, Flavin added, "is to try to find a practical way of producingcalanolide A." He explained: It's not going to be possible to have adrug without a practical source. So we're doing organic synthesis."[Editor's Note: The proposed exclusive license to MediChem will takeeffect 60 days after its imminent announcement in the Federal Register,barring valid objections. For licensing information concerning prostatinand its commercial development, contact licensing specialist StevenFerguson (301) 496-7735, ext. 266. Boyd is the principal inventor ofthe two calanolide pending patents, filed for in March 1992 and May1993. His patent application for prostatin is dated May 30, 1990.] n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.