Anti-Cancer Compounds from Bacteria Show Promise

Trioxacarcins disrupt cancer cell replication by binding and chemically-modifying genetic material.

A new process for the synthesis of anti-cancer agents originating in bacteria has been discovered by researchers at Rice University.

Trioxacarcins are found in the fermentation broth of Streptomyces bottropensis, a bacterial strain that disrupts the replication of cancer cells by binding and chemically modifying their genetic material.

“These molecules are endowed with powerful anti-tumor properties,” said lead researcher KC Nicolaou. “They are not as potent as shishijimicin, which we also synthesized recently, but they are more powerful than taxol, the widely used anti-cancer drug. Our objective is to make it more powerful through fine-tuning its structure.”

Normally, Nicolaou spends his time replicating rare and naturally occurring compounds and then fine-tuning their molecular structure through analog design and synthesis. This same procedure was used on trioxacarcins, and the results were published in the Journal of the American Chemical Society.

“Not only does this synthesis render these valuable molecules readily available for biological investigation, but it also allows the previously unknown full structural elucidation of one of them,” Nicolaou said. “The newly developed synthetic technologies will allow us to construct variations for biological evaluation as part of a program to optimize their pharmacological profiles.”

Currently, the researchers are teaming up with a biotechnology partner to pair payloads (cytotoxic compounds) with cancer-targeting antibodies through chemical linkers. This process will create antibody drug conjugates as treatments for cancer patients.

“It's one of the latest frontiers in personalized targeting chemotherapies,” Nicolaou said.