The First Efficient Synthesis of Natural Anticancer Ovatodiolide 2019.06.16

Recently, Angew. Chem, has published the latest breakthrough study on “cancer stem cell pharmaceutical chemistry ” conducted by Nankai University. The team led by Professor Chen Yue from National Key Pharmacy-Chemistry-Biology Laboratory and College of Pharmacy of Nankai University has completed the efficient chemical synthesis of Ovatodiolide for the first time and conducted experiment to prove such compound can kill liver cancer stem cells selectively, therefore, it has great potential to be made into drug.

Cancer stem cell (CSC) stands as the fundamental cause of cancer recurrence and metastasis in many cases so targeting at CSC will bring revolutionary improvement in cancer therapy. And drugs targeting at cancer stem cells are in urgent clinical demand. However, researchers have found out it’s hard to find compound that can kill CSC and there are few relevant natural substances, most of which have poor effects.

Viewing Ovatodiolide in absolute spatial configuration as the target molecule, Chen’s team has achieved the first complete synthesis of Ovatodiolide enantiomer and Isovatodiolide in 6-step divergent synthesis method by adopting two key serial strategies. This synthesis method is efficient and simple without using any protective genes and the weight of compound produced in this way can be measured by gram. With this complete synthesis, researchers has further confirmed and rectified the absolute spatial configuration of Ovatodiolide, Isovatodiolide and 4,5Epioxyovatodiolide. The compound synthesized by Chen’s team is enough for later antineoplastic activity research and the establishment of structure-activity relationship.

Chen’s team has primarily unveiled the structure-activity relationship in Ovatodiolide through the synthesis of Ovatodiolide derivatives and proven with experiment that Ovatodiolide can kill liver cancer stem cells.

According to researcher, Dr. Wang Liang, the experiment has proven that Isovatodiolide in low concentration (5 μM) can reduce the number of HepG2 stem cells. Under the same concentration condition, Isovatodiolide can better suppress tumor’s ability to produce microspheres than Ovatodiolide. But both have better inhibitory activity than the drug candidate targeting at CSC——ACT001, which is the primary original drug used to treat glioma in clinical trials at home and abroad.

The study was collectively funded by National Natural Science Foundation of China, Tianjin Natural Science Foundation and relevant programs launched by Nankai University. Co-authors include Professor Chen Yue, Dr. Wang Liang and Dr. Ding Yahui from Nankai University. The lead author is Xiang Junhong, a PhD student.

Source: Nankai News

Written by Wu Junhui

Edited by Translation Center, College of Foreign Languages

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