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Posts Tagged → alkaloid

A Toxic Tale Of Serendipity

This post is from guest blogger Lila Guterman, senior editor for C&EN’s Journal News & Community group, and was written for the “Our Favorite Toxic Chemicals” blog carnival.

I have long had a fondness for weird, complex, toxic natural products. (Witness three recent stories I assigned and edited.) So when ScienceGeist announced the “Our Favorite Toxic Chemicals” blog carnival, I knew I’d have to participate. It would give me the chance to tell the story of homobatrachotoxin.

The story begins in 1963, with a young NIH chemist, John W. Daly, taking a trip to Colombia at the request of his boss to investigate the chemistry of frog secretions. His discoveries would launch his career as a
chemical ecologist and pharmacologist, and would spur an outpouring of research into the toxin he discovered, batrachotoxin.

He published the chemical structure, the biological effects, and a partial synthesis, in 1971. Batrachotoxin and its natural analogs, homobatrachotoxin and batrachotoxinin A, are among the most toxic natural substances known. Just 200 ng kill a mouse in 8 minutes; the lethal dose for people is thought to be around 100 µg.

Daly and colleagues found that batrachotoxin binds to sodium channels, opening them. Researchers now use batrachotoxin to study how these channels interact with anesthetics, anticonvulsants, and antiarrhythmia agents.

Phyllobates terribilis. Credit: Micha Rieser

These alkaloid toxins are secreted by certain species of Colombian poison-dart frogs – so called because Indians in Western Colombia used their secretions to poison the tips of blow darts. The most poisonous frog, the bright yellow Phyllobates terribilis, secretes batrachotoxin at levels high enough to kill several people.

Daly developed an unorthodox method for deciding whether to collect a frog in the wild – one he was lucky, or prudent, enough not to try on Phyllobates terribilis: “It involved touching the frog, then sampling it on the tongue. If you got a burning sensation, then you knew this was a frog you ought to collect,” he told the NIH Record, in 2002. In his work with South and Central American frogs, Daly and his collaborators ended up isolating more than 500 new natural products. Continue reading →