Diels-Alder reaction between furan and maleic anhydride resulted in 5,6-dehydro norcantharidin, then norcantharidin was obtained by reduction. The substituted-carboxylic acid was condensed with N-aminothiourea in presence of phosphorus oxychloride, yielding 2-amino-1,3,4-thiadiazole derivatives. Novel norcantharidin derivatives were synthesized with acylation, then intramolecular condensation using norcantharidin (or 5,6-dehydro norcantharidin) and 2-amino- 1,3,4-thiadiazole derivatives. All the target compounds were confirmed by IR, (1)HNMR, ESI-MS and were reported for the first time. Norcantharidin derivatives antiproliferative assay was tested by MTT method against A549 and PC-3 cell lines. The results showed that all the norcantharidin derivatives displayed moderate inhibitory activities.

Acetyl-CoA carboxylase (ACC; EC 6.4.1.2) is the major enzyme of fatty acid synthesis and oxidation in response to dietary changes. In animals, there are two major isoforms of ACCs, ACC1 and ACC2, which are encoded by different genes and display distinct tissue and cellular distribution. We examined the effect of high concentration of arachidonic acid (AA) on the expression of ACC1 mRNA in HepG2 hepatoma cells cultured in the absence of insulin. After 12 h of treatment, AA was found to significantly up-regulate ACC1 mRNA level as well as that of cAMP regulatory element binding protein 1 (CREB1), implying the possible interactions between ACC1 and CREB1. In support of the hypothesis, several potential CREB1 binding sites were identified within the PII promoter of ACC1. Further experiments demonstrated that transient over-expression of CREB1 in HepG2 cells activates ACC1 PII promoter and induces the production of triacylglycerol in response to AA, indicating that the effect of AA on ACC1 is possibly regulated via CREB1.