Cancer Cell

Scientist at Rice University have developed and evaluated what they are calling tough yet tender cancer fighters.

The study and its findings are published in the Journal of the American Chemical Society wherein scientists describe development of analogs of potent anti-tumor agents known as epothilones using designs and methods that both improve their biological properties and simplify their manufacture.

Scientists say they have used substances that are similar in their cancer-fighting mechanism to paclitaxel, the drug for which he is best-known, but have superior properties. Some compounds of the dozens of variations the scientists created exhibit potent cytotoxicities against certain cancer cells, including a drug-resistant cell line.

Like the family of taxanes (of which paclitaxel is a member), epothilones prevent cancer cells from dividing by interfering with tubulin proteins that form the cells’ skeletal microtubules. Tests with kidney cancer and two human uterine sarcoma cell lines, one with multidrug resistance, showed that 10 of these new compounds were impressively potent against all three cell lines, the researchers reported.

The drugs are variations of epothilone B, a natural product isolated from Sorangium cellulosum, slime bacteria that live in soil. Scientists achieved the total synthesis of several of the natural products and related substances in the past, but those compounds proved too toxic to be used as anti-cancer drugs.

Just as important, scientists say, is the lab’s ability to add chemical “handles” to the molecules that allow them to be attached to drug-delivery systems like cancer-specific antibodies.

The team compared the reconfiguration of epothilone B, the starting material for their synthesis, with the transplant of body parts, as the team replaced components in the molecule to make the designed analogs more effective.

The strategy has been described as a kind of chemical surgery with the most important structural motif being the three-membered ring containing a nitrogen atom, a so-called aziridine moiety.

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