Design and Anticancer Evaluation of Novel Norcantharidin Derivatives with 3D-QSAR studies

Norcantharidin (NCTD) is a demethylated form of cantharidin (CAN) which was discovered from traditional Chinese medicine and is a treatment for cancers. In this study, two series of modification of CAN are designed and proposed based on the x-ray crystal structures of protein phosphatase 1 (PP1) and 2A (PP2A) which have been identified as molecular targets of CAN and NCTD for the anticancer activities. The synthesized compounds were tested by in vitro assays to verify the anticancer efficacy. Furthermore, the structure-activity relationship was discussed of the new efficacious compounds and their 3D-quantitative structure-activity relationship (3D-QSAR) was employed for further investigation on potent target molecules.