Anti-HIV and anti-cancer drugs derived from Borneo rainforest progressing to final development stages

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Anti-HIV and anti-cancer drugs derived from Borneo rainforest progressing to final development stages
mongabay.com
June 29, 2009

Two drugs derived from rainforest plants in Sarawk (Malaysian Borneo) are now in their final stages of development, reports Malaysian state media, Bernama.

Calanolide, an anti-HIV drug derived from the Bintangor or Calophyllum tree, is now in the clinical trial stage, said Deputy Chief Minister Tan Sri Dr George Chan, speaking to reporters in Miri, Sarawak at the launch of the official website for the Borneo Research Council Conference 2010.

Dr Chan said that samples of the anti-cancer drug Silvestrol were sent to the National Cancer Institute in the United States for testing.

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 Brazilian Amazon and Indonesia together have lost more than 120,000 square miles of forest in the past decade -- 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. 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's Botanical Garden which had in its possession several plants collected by the British over 100 years earlier. Sarawak banned the felling and export of Calophyllum shortly thereafter.

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.

Should either drug prove a commercial success, it would bolster the argument that standing rainforests have the potential to generate benefits beyond timber and agricultural land.

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