Synthesis, Antiproliferative Activity and DNA-Binding Properties of Nitrogen and Sulfur Heterocyclic Norcantharidin Acylamide Acid

Three novel norcantharidin acylamide acids (L1N-thiadiazole norcantharidin acylamide acid, C10H11N3O4S; L2N-thiazole norcantharidin acylamide acid, C11H12N2O4S and L3N-benzothiazole norcantharidin acylamide acid, C15H14N2O4S) were synthesized by the reactions of norcantharidin (NCTD7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylic acid anhydride, C8H8O4) with 2-amino-1,3,4-thiadiazole (C2H3N3S), 2-aminothiazole (C3H4N2S) and 2-aminobenzothiazole (C7H6N2S), respectively. Their structures were characterized by elemental analysis, IR, and NMR. The inhibition rates of L3 was much higher than those of L1 and L2 against human hepatoma cells SMMC7721 cell lines in vitro. The interaction between the compounds and DNA was studied by means of fluorescence quenching studies and viscosity measurements. The emission intensities decreased obviously with increasing concentration of the compounds in the fluorescence quenching experiments. The linear Stern-Volmer quenching constant Ksq values were 0.62 (L1), 0.55 (L2) and 1.08 (L3), respectively. The binding abilities followed the trend from high to low were L3, L1 and L2, respectively. The results of viscosity measurements showed that L1 and L2 might bind to DNA via partial intercalation, while L3 bound mainly in intercalation.