Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of 2-hydroxy-1H-isoindolediones as new cytostatic agents.
A series of 16 derivatives of 2-hydroxy-1H-isoindole-1,3-diones was designed and synthesized as potential antitumor agents. The cytostatic activity against L1210 cell growth of these compounds was studied, and their IC50 values were found to be in the range of 10(-4) to 10(-8) M. Quantitative structure-activity relationship analysis of these compounds showed that the inhibitory effect was well correlated with the electronic and the lipophilic parameters. Derivatives having a substituent with strongly electron-donating properties at the 6-position showed enhanced inhibitory activity while compounds having an electron-withdrawing group at the same position showed lower activity.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D007211:Indoles / Q000138:chemical synthesis* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007211:Indoles