title: Synthesis and cytotoxic activity of benzo[a]acronycine and benzo[b]acronycine substituted on the A ring.
abstract: The impact of substitutions at position 10 in the A ring of the cytotoxic benzo[a]acronycine and benzo[b]acronycine series has been explored. 10-Bromobenzo[a] and 10-bromobenzo[b]acronycine were prepared in 12% and 15% yield respectively from commercially available chemicals. Their 1,2-dihydro-1,2-dihydroxy diesters were synthesized. The different derivatives were tested against two cell lines KB-3-1 and L1210. Their cytotoxic activities were found in the same range of magnitude as their non-substituted counterparts. These structure-activity relationships permitted to conclude that the introduction of a substituent at position 10 maintains the activity in both the benzo[a] and [b]acronycine series and open the way to further pharmacomodulations.
authors.affiliation: Laboratoire de Pharmacognosie, Université Paris Descartes, UMR/CNRS 8638, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75006 Paris, France. thomas.gaslonde@parisdescartes.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Gaslonde
authors.forename: Fabiola
authors.initials: F
authors.lastname: Covello
authors.forename: Laura
authors.initials: L
authors.lastname: Velazquez-Alonso
authors.forename: Stéphane
authors.initials: S
authors.lastname: Léonce
authors.forename: Alain
authors.initials: A
authors.lastname: Pierré
authors.forename: Bruno
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: Sylvie
authors.initials: S
authors.lastname: Michel
authors.forename: François
authors.initials: F
authors.lastname: Tillequin
mesh_terms: D000175:Acronine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C504489:benzo(b)acronycine; D000175:Acronine