[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: S Giorgi-Renault
• Journal: Annales pharmaceutiques francaises (Ann Pharm Fr) Vol. 63 Issue 1 Pg. 63-8 (Jan 2005) ISSN: 0003-4509 [Print] France
• Vernacular Title: 4-aza-2,3-didéhydropodophyllotoxines: nouveaux lignanes à activité antitumorale obtenus par une synthèse en une seule étape.
• PMID: 15803102 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antineoplastic Agents
• Aza Compounds
• Podophyllotoxin

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Aza Compounds (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Humans
• Mice
• Microtubules (drug effects)
• Podophyllotoxin (analogs & derivatives, chemical synthesis, pharmacology)
• Structure-Activity Relationship