Inspired by a chemical that fungi use to defend their territory, researchers at MIT and the University of Illinois at Urbana-Champaign (UIUC) have designed and tested 60 compounds derived from a fungus for their ability to kill human cancer cells - and excitingly, some of them were found to be quite potent.

Many of the compounds tested are naturally produced by fungi and may help them prevent other organisms from encroaching on their territory.

Additionally, the researchers created even more compounds to test against cancer by systematically adding or removing certain chemical groups from different locations on the structures of the original compounds.

First, 60 compounds were prepared and tested against cell lines derived from human cervical cancer and lymphoma. Then the researchers picked the best 25 to test against three additional lines, from lung, kidney and breast tumors.

Typically, these natural compounds are made up of least one set of fused rings containing one or more sulfur atoms. The key to their tumor-killing ability was revealed to be the arrangement and number of these sulfur atoms: compounds with at least two sulfur atoms were the most effective, those with only one sulfur atom were less effective, and those without sulfur did not kill tumor cells efficiently.

Promisingly, those compounds that killed cancer cells destroyed them 1,000 times more effectively than they killed healthy blood cells.

This study reveals for the first time a number of relationships between the chemical structures of anticancer compounds and how they may actually work. This knowledge will be essential for their future development into attractive clinical candidates and potential anticancer drugs.

With this initial data, the researchers can now design more compounds that are even more effective. They can test their ideas in terms of which parts of the structures of these compounds are the most useful in terms of keeping or further improving their anticancer activity.



Natural Fungal Compounds with Anticancer Activity