title: Synthesis, cytotoxic activity, and DNA binding properties of antitumor cis-1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine cinnamoyl esters.
abstract: Monocinnamoyl esters at position 2 of (+/-)-cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one and their acetyl derivatives at position 1 were prepared as stabilized analogues of the anticancer alkylating agent S23906-1. Monocinnamoyl esters at position 2 were slower DNA alkylators than the reference 2-monoacetate. Mixed esters bearing an acetyl ester group at position 1 and a cinnamoyl ester group at position 2 alkylated DNA slower than S23906-1. A strong correlation was observed between cytotoxicity and DNA alkylation kinetics, with slower alkylators displaying more potent antiproliferative activities. The most cytotoxic compounds proved to be significantly active in vivo against murine C-38 adenocarcinoma implanted in mice, but less potent than S23906-1.
authors.affiliation: Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacognosie de l'Université Paris Descartes, UMR/CNRS No 8638, Paris, France.
authors.forename: Quyên
authors.initials: Q
authors.lastname: Do
authors.forename: Wen
authors.initials: W
authors.lastname: Tian
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Yougnia
authors.forename: Thomas
authors.initials: T
authors.lastname: Gaslonde
authors.forename: Bruno
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: Alain
authors.initials: A
authors.lastname: Pierré
authors.forename: Stéphane
authors.initials: S
authors.lastname: Léonce
authors.forename: Laurence
authors.initials: L
authors.lastname: Kraus-Berthier
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: David-Cordonnier
authors.forename: Sabine
authors.initials: S
authors.lastname: Depauw
authors.forename: Amélie
authors.initials: A
authors.lastname: Lansiaux
authors.forename: Romain
authors.initials: R
authors.lastname: Mazinghien
authors.forename: Michel
authors.initials: M
authors.lastname: Koch
authors.forename: François
authors.initials: F
authors.lastname: Tillequin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Michel
authors.forename: Hanh
authors.initials: H
authors.lastname: Dufat
mesh_terms: D000175:Acronine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; C436732:S 23906-1; D004247:DNA; D000175:Acronine