Macrocyclic drug conjugates of metronidazole-cyclodextrin for colon-targeted delivery

Abstract

New podophyllotoxin C4-derivatives with bridged and cage moieties were synthesized by the Steglich esterification of podophyllotoxin with polycyclic carboxylic acids or by etherication with (adamantan-1-yl)methanol in the presence of BF3·Et2O with the following separation of diastereomers. Most of the target compounds inhibited the growth of human lung carcinoma A549 cells, induced apoptosis, stimulated shortening of microtubules or induced their unusual curling and involution. The activity depends on the slightest differences in the structures of alicyclic moieties and the type of the bond between podophyllotoxin and alicyclic group.