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

作　　者：Wang, Na Wang, Yunyun Wang, Xiaoxia Zheng, Xiaoliang Yan, Dongmei Lin, Qiuyue[1,2] 

机构地区：[1]College of Chemical and Life Science, Zhejiang Normal University, Jinhua, Zhejiang 321004, China [2]Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, Zhejiang Normal University, Jinhua, Zhejiang 321004, China [3]Institute ofMateria Medica of Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, China

出　　处：《Chinese Journal of Chemistry》2011年第3期473-477,共5页中国化学（英文版）

基　　金：Project supported by the Natural Science Foundation of-Zhejiang Province, China （No. Y407301）.

摘　　要：Three novel norcantharidin acylamide acids （L1 =N-thiadiazole norcantharidin acylamide acid, CIoHIlN304S; L2=N-thiazole norcantharidin acylamide acid, CjIHI2N204S and L3=N-benzothiazole norcantharidin acylamide acid, C15H14N204S） were synthesized by the reactions of norcantharidin （NCTD=7-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 Lj 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 （Ll）, 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.Three novel norcantharidin acylamide acids （L1 =N-thiadiazole norcantharidin acylamide acid, CIoHIlN304S; L2=N-thiazole norcantharidin acylamide acid, CjIHI2N204S and L3=N-benzothiazole norcantharidin acylamide acid, C15H14N204S） were synthesized by the reactions of norcantharidin （NCTD=7-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 Lj 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 （Ll）, 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.

关 键 词：NORCANTHARIDIN DNA fluorescence spectroscopy antiproliferative activity 

分 类 号：O636.1[理学—高分子化学] TB333[理学—化学]