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Calanolide A

Scientific Name(s): Calophyllum lanigerum var. austrocoriaceum
Common Name(s): Calanolide A

Clinical Overview

See also: Atripla

Use

Calanolide has demonstrated antimicrobial activity, and interest focuses on applications in HIV; however, clinical studies are lacking.

Dosing

Calanolide A is an investigational anti-HIV drug that has been given in early clinical trials at an oral dose of 200 to 800 mg; however, it is not available for use. Its safety and efficacy remain to be defined.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Because this product is a relatively new discovery, no data are available.

Toxicology

Calanolide A is an investigational anti-HIV drug. Its safety and efficacy remain to be defined.

Botany

Calanolide A is a compound isolated from the latex of the tree Calophyllum lanigerum var. austrocoriaceum that grows in the rain forest of the Malaysian state of Sarawak on the island of Borneo. There are at least 200 species in the genus Calophyllum.McKee 1998, Shenon 1994, USDA 2016

History

Rain forests are a very promising source of natural medicines because of their vast diversity. It has been estimated that more than half of the world's 250,000 plant species exist in tropical rain forests. Searching for natural drugs in these areas, the National Cancer Institute (NCI) contracts scientists to gather specimens for analysis. In 1987, an Illinois team obtained samples from many trees, one of which was Calophyllum lanigerum. Four years later, the NCI discovered that a preparation from this gum tree was active against the human immunodeficiency virus type 1 (HIV-1).Defant 2015, Shenon 1994

Chemistry

Plants from the genus Calophyllum have been shown to contain xanthones, steroids, triterpenes, coumarins, and benzopyrans. Calanolide A is considered a dipyranocoumarin, with nonnucleoside HIV-1 specific reverse transcriptase inhibiting properties. McKee 1998, McKee 1996 Many studies in this area discuss findings from the genus Calophyllum, and offer structural representations, related compounds and their derivatives, modifications of the molecule, etc.Galinis 1996, Kashman 1992, Ma 2008, McKee 1998, McKee 1996, Sekino 2004, Yu 2007, Zembower 1997 Calanolide A has been synthesized in the lab and was found to have similar actions to the natural product.Flavin 1996

Uses and Pharmacology

Antiviral activity

Calanolide A and other related compounds from the genus Calophyllum have demonstrated antiviral activity including nonnucleoside reverse transcriptase inhibition,Matthee 1999, Newman 1998 and activity against influenza H3N1 and H1N1 viruses.Rajasekaran 2013

Animal data

Early interest in Calophyllum extracts in the management of HIV infections persists,Matthee 1999, Newman 1998 particularly as an option for clinically relevant mutant HIV strains.Usach 2013

Clinical data

Calanolide A is being investigated in phase I clinical trials for safety, tolerability, and pharmacokinetics.Creagh 2001, Usach 2013

Other effects

Calanolide A is being investigated as an anti-tumor agentDefant 2015 and for activity against Mycobacterium tuberculosis.Liu 2015

Dosing

Calanolide A is an investigational anti-HIV drug that has been given in early clinical trials at an oral dose of 200 to 800 mg; however, it is not available for use. Safety and efficacy remain to be defined.Creagh 2001

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Information is limited.Creagh 2001, Usach 2013

Toxicology

Information is limited.

References

Creagh T, Ruckle JL, Tolbert DT, et al. Safety and pharmacokinetics of single doses of (+)-calanolide a, a novel, naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy, human immunodeficiency virus-negative human subjects. Antimicrob Agents Chemother. 2001;45:1379-1386.11302799
Defant A, Mancini I, Tomazzolli R, Balzarini J. Design, synthesis, and biological evaluation of novel 2H-pyran-2-one derivatives as potential HIV-1 reverse transcriptase inhibitors. Arch Pharm (Weinheim). 2015;348(1):23-33.25523431
Flavin M, et al. Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers. J Med Chem. 1996;39(6):1303-13.8632437
Galinis D, et al. Structure-activity modifications of the HIV-1 inhibitors (+)- calanolide A and (-)-calanolide B. J Med Chem. 1996;39(22):4507-10.8893846
Genus Calophyllum L. USDA, NRCS. 2016. The PLANTS Database (http://plants.usda.gov, September 2016). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accesssed September 2016.
Kashman Y, et al. The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum. J Med Chem. 1992;35(15):2735-43.1379639
Liu Z, Guo X, Liu G. Modified calanolides incorporated with furan-2-nitro mimics against Mycobacterium tuberculosis. Bioorg Med Chem Lett. 2015 Mar 15;25(6):1297-300. doi: 10.1016/j.bmcl.2015.01.04625681226
Ma T, Liu L, Xue H, et al. Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents. J Med Chem. 2008;51(5):1432-1446.18284187
Matthee G, et al. HIV reverse transcriptase inhibitors of natural origin. Planta Med. 1999;65(6):493-506.10483367
McKee T, et al. New pyranocoumarins isolated from Calophyllum lanigerum and Calophyllum teysmannii. J Nat Prod. 1996;59:754–58.8792623
McKee T, et al. Pyranocoumarins from tropical species of the genus Calophyllum: A chemotaxonomic study of extracts in the National Cancer Institute Collection. J Nat Prod. 1998;61:1252-56.9784162
Newman R, et al. Pharmaceutical properties of related calanolide compounds with activity against human immunodeficiency virus. J Pharm Sci. 1998;87(9):1077-80.9724557
Rajasekaran D, Palombo EA, Chia YT, et al. Identification of traditional medicinal plant extracts with novel anti-influenza activity. PLoS ONE. 2013;8(11):e79293.
Sekino E, Kumamoto T, Tanaka T, Ikeda T, Ishikawa T. Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition. J Org Chem. 2004;69(8):2760-2767.15074925
Shenon P. Hunt in forests of Borneo aims to track down natural drugs. New York Times. 1994 Dec 6.
Usach I, Melis V, Peris JE. Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. J Int AIDS Soc. 2013 Sep 4;16:1-14. doi: 10.7448/IAS.16.1.18567.24008177
Yu D, Morris-Natschke SL, Lee KH. New developments in natural products-based anti-AIDS research. Med Res Rev. 2007;27(1):108-132.16888749
Zembower D, et al. Structural analogues of the calanolide anti-HIV agents. Modification of the trans-10,11-dimethyldihydropyran-12-0l ring (ring C). J Med Chem. 1997;40(6):1005-17.9083491

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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