4-aza-2,3-dehydro-4-deoxypodophyllotoxins: Simple aza-podophyllotoxin analogues possessing potent cytotoxicity

4-Aza-2,3-dehydro-4-deoxypodophyllotoxin analogues 3a-n were synthesized through quinolines 2a-n. Comparison of their cytotoxicity against P-388 leukemia cells revealed that the steric effects of the ring B substituents on the activity are greater than the electronic effects, while the presence of a methoxy group on the ring E is not essential to exhibit potent cytotoxicity. Analogues 3a and 3b proved to be more than twice as cytotoxic as natural podophyllotoxin (1). (C) 2000 Elsevier Science Ltd. All rights reserved.