Saving What Remains
ANTI-HIV COMPOUNDS FROM THE RAINFOREST
(Sarawak MediChem Pharmaceuticals, Inc. 1998)
Calanolide A was isolated from a Borneo tree species by the National Cancer Institute (NCI). In vitro studies have shown Calanolide A, a non-nucleoside reverse transcript inhibitor "to be active against HIV-1, including strains resistant to AZT, Nevirapine, and other nucleoside reverse transcriptase inhibitors." The compound has also shown to be effective in combination with other anti-HIV drugs like AZT, ddI, ddC, Nevirapine, and Carbovir. Calanodine A has been shown in animal studies to enter viral reservoir sites "by crossing the blood-brain barrier and accumulating in the lymph nodes."
Researchers are grateful that Calanolide A even came into existence. Calanolide A is derived from Calophyllum lanigerum var austrocoriaceum, an exceedingly rare member of the Guttiferae or mangosteen family. Samples of Calophyllum lanigerum var austrocoriaceum were first collected in 1987 on an NCI-sponsored expedition in Sarawak, Malaysia on the island of Borneo. Once it was determined that Calophyllum lanigerum var austrocoriaceum showed activity against HIV, researchers returned to the original kerangas forest near Lundu (Sarawak, Malaysia) to gather more plant matter for isolating the active compound. The tree was gone -- likely felled by locals for fuelwood or building material. The disappearance of the tree lead to mad search by botanists for further specimen. Good news finally came from the Singapore Botanic Garden which had several plants collected by the British over 100 years earlier. Sarawak banned the felling and export of Calophyllum shortly thereafter.
Due to the low prevalence of Calanolide A in Calophyllum lanigerum var austrocoriaceum (only 0.05% can be extracted from the twigs and leaves) MediChem Research, Inc., has developed and patented a process for the total synthesis of (+)-Calanolide A. Calanolide A is currently in clinical trials. Details can be found at http://www.herbmed.org/Herbs/Herb19.htm and http://www.aidsmeds.com/drugs/calanolide-A.htm
A related species, Calophyllum teysmannii var. inophylloide, produces a compound (Costatolide) that also exhibits activity against HIV. Costatolide, now known as (-)-Calanolide B, is present in the latex so that tree need not be felled in order to collect the compound.
Hanna, L. "Calanolide A: A Natural Non-Nucleoside Reverse Transcriptase Inhibitor." Bulletin of Experimental Treatments for AIDS. April 1999.
Sarawak MediChem Pharmaceuticals, Inc. PRNewswire. February 5, 1998; September 30, 1998.
Wilson, E.O. The Future of Life. Alfred A. Knopf. New York: 2002.
Derived from Ancistrocladus korupensis, a liana species discovered by NCI in 1987 in Korup National Park in southwestern Cameroon, Michellamine B shows in vitro activity against HIV-1 and HIV-2 by acting "at two distinct stages of the HIV life cycle: inhibiting both viral fusion and reverse transcriptase (RT). Unlike many other non-nucleoside RT inhibitors, Michellamine B inhibits the enzymatic activity of both HIV-1 and HIV-2 reverse transcriptase." (NIH 2002). For more, including the molecular structure of Michellamine B, check out http://www.niaid.nih.gov/daids/dtpdb/003610.htm
Boyd, M.R., Y.F. Hallock, J.H. Cardellina II, K.P. Manfredi, J.W. Blunt, J.B. McMahon, R.W. Buckheit, Jr., G. Bringmann, M. Schäffer, G.M. Cragg, D.W. Thomas, and J.G. Jato. 1994. Anti-HIV michellamines from Ancistrocladus korupensis. J. Med. Chem. 37: 1740-1745.
Manfredi, K.P., J.W. Blunt, H.H. Cardellina II, J.B. McMahon, L.L. Pannell, G.M. Cragg, and M.R. Boyd. 1991. J. Med. Chem. 34: 3402-3405.
MCMAHON, J.B.; CURRENS, M.J.; GULAKOWSKI, R.J.; BUCKHEIT JR, R.W.; LACKMAN-SMITH, C.; HALLOCK, Y.F.; BOYD, M.R., MICHELLAMINE B, A NOVEL PLANT ALKALOID, INHIBITS HUMAN IMMUNODEFICIENCY VIRUS-INDUCED CELL KILLING BY AT LEAST TWO DISTINCT MECHANISMS. ANTIMICROB AGENTS CHEMOTHER 39(2):484-488 (1995).
Thomas, D.W., M.R. Boyd, R.E. Gereau, J. Jato, and P. Symonds. 1994. Sustainable harvest of Ancistrocladus korupensis (Ancistrocladaceae) leaf litter for research on HIV. Econ. Bot. 48: 413-414.
Thomas, D.W. and R.E. Gereau. 1993. Ancistrocladus korupensis (Ancistrocladaceae): a new species of liana from Cameroon. Novon 3: 494-498.
More HIV/AIDS resources at mongabay.com:
Table showing the impact of AIDS on life expectancy in the Developing World
Origin of HIV-AIDS
Editorial proposing estimates of AIDS deaths may be exaggerated
AIDS is leading cause of death for South African women [The Wall Street Journal]
FDA fast-tracks HIV vaccine [The Wall Street Journal]
AIDS vaccine trials [The Wall Street Journal]
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