title: [4-Aza-2,3-didehydropodophyllotoxins: new lignan with antitumor activity obtained from one-step synthesis].
abstract: Podophyllotoxin, a natural lignan, is a good inhibitor of tubulin polymerization with antitumoral properties but it is too toxic for therapeutic use. In order to obtain less toxic drugs, several heterolignans have been prepared. We presented the synthesis and preliminary pharmacological properties of 4-aza-2,3-didehydropodophyllotoxins (dihydropyrrole [3,4-b]quinolin-1-ones), a new azalignan series. A straightforward synthesis was described according to a multicomponent reaction in a one-pot procedure. Starting from an aniline, an aromatic aldehyde, and a cyclic B-diketone, many substituted analogues could be prepared. Our lead, the 4-aza-2,3-didehydropodophyllotoxin, is extremely cytotoxic on various tumor cell lines, active in vivo on murine tumors. Like podophyllotoxin, this drug inhibits microtubule assembly without any effect on depolymerization.
authors.affiliation: Laboratoire de chimie thérapeutique, Umr Cnrs-Université René Descartes n degree 8638, Faculté des sciences pharmaceutiques et biologiques, 4, avenue de l'Observatoire, F75270 Paris Cedex 06, France.
authors.forename: S
authors.initials: S
authors.lastname: Giorgi-Renault
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001372:Aza Compounds; D011034:Podophyllotoxin