New chemistry from tropical corals

It's a long way -- geographically and taxonomically -- from a shrub in the forests of the Pacific Northwest to a coral on a reef off western Australia, but the two share some unusual chemistry. Like the anticancer drug Taxol, derived from the Pacific yew, a compound manufactured by the rare Eleutherobia coral gums up the internal scaffolding of a cell.

 The coral compound, eleutherobin, joins a select class of chemicals known to exert such an effect. Researchers from the Scripps Institution of Oceanography in La Jolla, Calif., and Bristol-Myers Squibb in Princeton, N.J., describe the compound's structure in the Sept. 17 Journal of the American Chemical Society. Although eleutherobin's basic structure is built of five-carbon rings, as is Taxol's, the compounds have no further similarities, says William H. Fenical of Scripps.

 Eleutherobin is the latest of numerous new drug candidates that have been extracted from marine organisms in recent years. The diverse organisms that have coevolved on a coral reef are prime targets in biochemical prospecting. Many can't flee from predators, so they ward them off with chemicals that may be adapted for therapeutic uses. So far, eleutherobin has been tested only on human cell lines grown in the laboratory, but it seems to be extremely potent against breast, renal, ovarian, and lung cancer cells, says Fenical. Details of its biological activity are slated for publication in Cancer Research, he adds.

 Fenical collected the yellow or red pinkie-size coral on a 1993 trip to study chemical defenses. "We weren't looking for cancer drugs," he says, but a routine screening indicated that something in the corals could kill cells. Corals are a known source of anti-inflammatory agents -- one is marketed in a skin cream. Patented in 1995, eleutherobin is licensed to Bristol-Myers Squibb, which markets Taxol.

 Eleutherobin's ability to gum up a cell's microtubules and thereby stop it from dividing is a "very intriguing activity," says David J. Newman of the National Cancer Institute in Frederick, Md. However, few of the natural compounds that show promise in the lab make it through animal and human testing onto the market. Eleutherobin, says Newman, "has overcome a major hurdle, but it's got a long way to go."

 Rarely is a specific natural product of pharmaceutical interest, says Newman: "We're not looking for drugs, we're looking for structures." The basic structure of the AIDS drug AZT, for example, was identified in a sponge, he notes.

 Marketability may be a gamble, but the novelty of coral chemistry is a sure bet. Researchers from Vanderbilt University in Nashville and their colleagues report the unusual structure and function of another chemical, from a Caribbean sea whip, in the Sept. 26 Science. That enzyme may be involved in the coral's synthesis of compounds resembling prostaglandins, hormones that exist in minute amounts in people but make up 2 to 3 percent of the coral's dry weight. Their function in coral is unknown.