Synthesis And In Vitro Antitumor Activity Of The Norcantharidin Derivatives

Cantharidin is a rich source of potential anticancer agents of Traditional Chinese medicine. In recent studies, it has been found that cantharidin possesses many properties of anti-cancer, anti-inflammatory and increasing the number of leucocytes and et al. But its toxicity is very high, it can make people easily poisoned and even die if used inappropriately which prevented it from using in mainstream oncology. What is more, synthesis of cantharidin needs extremely high pressure, which makes it impossible produce in industry. In constrast, norcantharidin possesses nearly the same anti-cancer activity as cantharidin. And it possesses relatively low toxicity and also can be synthesized easily. However, there is still some toxicity when the dose is increased, which affect its anti-cancer effect. Therefore, design and synthesis of a number of norcantharidin derivatives of selective inhibition to tumor cells, but small toxicity and less effect on the immune response is of great significance.2-amino-1,3,4-thiadiazole derivatives have widely biological activity, many anti-cancer tests showed that they had good effects against cancer, is an important kind intermediates in the research and development of a new drug,with a hybrid pharmacophore approach, taking dehydronorcantharidin and norcantharidin the leading compound, a series of novel dehydronorcantharidin amic acid and norcantharidin amic acid derivatives, dehydronorcantharidimide and norcantharidimide derivatives were designed and synthesized. In the whole design scheme, the di-ring [2,2,1] heptanes skeleton was retained, we mainly carried out structure modification focusing on the five-anhydride-ring. Their structures are confirmed by IR, ESI-MS and 1H NMR, all the compounds are novel without reported in previous literature. Preliminary bioactivity assays are carried out in vitro and have attained the data of imide derivatives’antitumor activity to A549 and PC-3. The results show that all the imide derivatives we have synthesized have weak inhibitions with A549 and PC-3.