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 th rough quinolines 2a-n. Comparison of their cytotoxicity against P-388 leuke mia cells revealed that the steric effects of the ring B substituents on th e activity are greater than the electronic effects, while the presence of a methoxy group on the ring E is not essential to exhibit potent cytotoxicit y. Analogues 3a and 3b proved to be more than twice as cytotoxic as natural podophyllotoxin (1). (C) 2000 Elsevier Science Ltd. All rights reserved.