- Rainforest plants have long been recognized for their potential to provide healing compounds.
- Indigenous peoples of the rainforest have used medicinal plants for treating a wide variety of health conditions while western pharmacologists have derived a number of drugs from such plants.
- However, as forests around the world continue to fall there is a real risk that pharmaceutically-useful plants will disappear before they are examined for their chemical properties.
- Increasingly, it is becoming a race against time to collect and screen plants before their native habitats are destroyed. One near miss occurred recently with a compound that has shown significant anti-HIV effects, Calanolide A.
Rainforest plants have long been recognized for their potential to provide healing compounds. Indigenous peoples of the rainforest have used medicinal plants for treating a wide variety of health conditions while western pharmacologists have derived a number of drugs from such plants.
However, as forests around the world continue to fall — the Amazon alone has lost more than 200,000 miles of forest since the 1970s — there is a real risk that pharmaceutically-useful plants will disappear before they are examined for their chemical properties. Increasingly, it is becoming a race against time to collect and screen plants before their native habitats are destroyed. One near miss occurred recently with a compound that has shown significant anti-HIV effects, Calanolide A.
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 a National Cancer Institute (NCI)-sponsored expedition in Sarawak, Malaysia on the island of Borneo. Once scientists 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.
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. Calanolide A has been shown in animal studies to enter viral reservoir sites “by crossing the blood-brain barrier and accumulating in the lymph nodes.”
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are a class of anti-HIV drugs that prevent healthy T-cells in the body from becoming infected with HIV. Approved NNRTIs include Viramune® (nevirapine) from Boehringer Ingelheim, Sustiva® (efavirenz) from Bristol-Myers Squibb, and Rescriptor® (delavirdine) from Pfizer. Most NNRTIs dramatically reduce viral load soon after the first dose is taken, but Calanolide A, for reasons that are not yet known, seems to have a delayed effect.
Due to the low prevalence of Calanolide A in Calophyllum lanigerum var austrocoriaceum (only 0.05% can be extracted from the twigs and leaves) Sarawak MediChem Pharmaceuticals, has developed and patented a process for the total synthesis of (+)-Calanolide A. Calanolide A is currently in clinical trials but is not yet approved by the FDA for use outside of clinical trials..
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. Calanolide B is in preclinical testing with the National Cancer Institute.
What Calanolide A and Calanolide B could demonstrate is that rainforests are a critical resource for reasons beyond the ecological services they provide (carbon storage, role in water cycle, erosion mitigation, storehouse of biodiversity, etc). Rainforests have the potential to generate economic benefit to a number of stakeholders — the people who reside in them, the governments that control the land, and outside firms and organizations who have the technology to develop drug candidates from plants found within. Protecting rainforests that remain is our choice. Before we allow them to disappear, it would be wise to consider the consequences of losing these irreplaceable resources with unknown potential benefits.
On October 1, 2019 a broken image was replaced with the image showing burned peatlands in Indonesia.