Synthesis of l-ascorbic acid-amino acid-norcantharidin conjugates and their biological activity evaluation in vitro.

Three components of L-ascorbic acid, amino acid and functionalized norcantharidins were constructed together in several steps to form 42 norcantharidin derivatives in a high yield. The structure of these synthesized l-ascorbic acid-amino acid-norcantharidin conjugates are determined by 1 HNMR, 13 CNMR and MS spectrum. The results showed that compounds 6e , 6g , 6j , 6l , 6m , 6b , 6e , 6i , and 6n showed high cytotoxicity to HepG2 and compounds 6b , 6e-g , 6l , 6n , 7b , 7d , 7h , 7i , 7n , 8g , 8i exhibited high cytotoxicity to SW480; Meanwhile, besides 6b , 6e , 6g , and 6k , the other compounds showed less toxic to LO2 at a concentration of 50 μg/mg after 72 h. Compound 6g can induce Mφ-type macrophages derived from mouse bone marrow to polarize to M1-type macrophages.