Design of 92 New 9-Norlignan Derivatives and Their Effect on Cell Viabilities of Cancer and Insect Cells

摘要

Ninety-two new 9-norlignan derivatives containing more effective compounds against both cancer and insect cells than lead compounds were synthesized. Against HeLa cells, 7-(3,4-dimethoxyphenyl)-7'-(3'-hydroxy-4'-methoxyphenyl) derivative 63 (IC50 = 0.9 +/- 0.2 mu M) was to be around 6-fold more potent than lead compound 5. Moreover, against HL-60 cells, 7-(4-trifluoromethylphenyl)-7'-(374'-hydroxyphenyl) derivatives 78 and 79 (IC50 = 2.2 +/- 0.4 mu M and 2.4 +/- 0.6 mu M) were 3-fold more potent than lead compound 5. Furthermore, against Sf9 cells from the common cutworm, the 7-(4-trifluoromethylphenyl) derivatives bearing electron-withdrawing groups 76-96 showed a wider range of activity (around 20-fold difference), giving valuable information on the structure-activity relationship. The 7-(4-trifluoromethylphenyl)-7'-(2'/3'-hydroxyphenyl) derivatives 77 and 78 (IC50 = 4.7 +/- 0.6 mu M and 4.9 +/- 0.9 mu M) had around 2-fold higher activity against Sf9 cells than lead compound 5. The 7-(4-trifluoromethylphenyl)-7'-(3'-hydroxyphenyl) derivative 78 was also effective against mosquito NIAS-AcAl-2 cells with an IC50 value of 5.4 +/- 0.3.