title: 4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: simple aza-podophyllotoxin analogues possessing potent cytotoxicity.
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).
authors.affiliation: Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hitotsuyanagi
authors.forename: M
authors.initials: M
authors.lastname: Fukuyo
authors.forename: K
authors.initials: K
authors.lastname: Tsuda
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: A
authors.initials: A
authors.lastname: Ozeki
authors.forename: H
authors.initials: H
authors.lastname: Itokawa
authors.forename: K
authors.initials: K
authors.lastname: Takeya
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007641:Keratolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003603:Cytotoxins; D007641:Keratolytic Agents; D011804:Quinolines; D015363:Quinolones; D011034:Podophyllotoxin