Rice University scientists have achieved the total synthesis of a scarce natural marine product that may become a powerful cancer-fighting agent – the molecule shishijimicin A.
A group led by world-renowned Rice chemist K.C. Nicolaou announced the successful synthesis this month in the Journal of the American Chemical Society.
The complex organic molecule was discovered in a rare sea squirt, Didemnum proliferum, more than a decade ago. Lab tests at the time proved it to be more than 1,000 times as toxic to cancer cells as the anticancer drug taxol (aka paclitaxel), but its scarcity did not provide amounts sufficient for extensive biological studies and clinical trials.
Nicolaou said the next steps for shishijimicin are to streamline its synthesis and add chemical handles so it can be attached to antibodies for delivery to cancer cells. “We’ve established the beachhead with the first total synthesis,” he said. “Now we aim to optimize the process to make it more practical and apply it to synthesize variations of the molecule.”
Then it will be up to partner pharmaceutical companies to develop the compound for eventual clinical trials. They won’t need much, Nicolaou said. “If they have a few hundred milligrams – a fraction of a gram – they can take it to clinical trials, because it’s so potent,” he said. “And now they have hundreds of antibodies selected for different kinds of cancer. My hope is that our molecule will lead to an effective drug for personalized medicine.”
The Cancer Prevention and Research Institute of Texas and the Welch Foundation supported the research.