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

  • Bioorg Med Chem Lett. 2000 Feb 21;10(4):315-7. doi: 10.1016/s0960-894x(99)00693-9.
Y Hitotsuyanagi  1 ,  M Fukuyo ,  K Tsuda ,  M Kobayashi ,  A Ozeki ,  H Itokawa ,  K Takeya
Affiliations
  • 1. Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
PMID: 10714489 DOI: 10.1016/s0960-894x(99)00693-9
Abstract

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).