title: Semisynthesis, cytotoxic activity, and oral availability of new lipophilic 9-substituted camptothecin derivatives.
abstract: Despite that 9-substituted camptothecins are promising candidates in cancer therapy, the limited accessibility to this position has reduced the studies of these derivatives to a few standard modifications. We report herein a novel semisynthetic route based on the Tscherniac-Einhorn reaction to synthesize new lipophilic camptothecin derivatives with amidomethyl and imidomethyl substitutions in position 9. Compounds were evaluated for their antiproliferative activity, topoisomerase I inhibition, and oral availability. Preliminary data demonstrated that bulky imidomethyl modification is an appropriate lipophilic substitution for an effective oral administration relative to topotecan. In addition, this general procedure paves the way for obtaining new camptothecin derivatives.
authors.affiliation: Instituto Mixto de Tecnología Química, Universidad Politécnica de Valencia-Consejo Superior de Investigaciones Científicas (UPV-CSIC) , Avd. de los Naranjos s/n, 46006 Valencia, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Rodriguez-Berna
authors.affiliation: Instituto Mixto de Tecnología Química, Universidad Politécnica de Valencia-Consejo Superior de Investigaciones Científicas (UPV-CSIC) , Avd. de los Naranjos s/n, 46006 Valencia, Spain.
authors.forename: Maria Jose Díaz
authors.initials: MJ
authors.lastname: Cabañas
authors.affiliation: Depto. de Ingeniería, Área Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández , Carretera Alicante-Valencia km. 87, 03550 San Juan, Alicante, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Mangas-Sanjuán
authors.affiliation: Depto. de Ingeniería, Área Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández , Carretera Alicante-Valencia km. 87, 03550 San Juan, Alicante, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gonzalez-Alvarez
authors.affiliation: Depto. de Ingeniería, Área Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández , Carretera Alicante-Valencia km. 87, 03550 San Juan, Alicante, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonzalez-Alvarez
authors.affiliation: CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebrón and Vall d'Hebrón Institut de Recerca, Universitat Autónoma de Barcelona , 08035 Barcelona, Spain.
authors.forename: Ibane
authors.initials: I
authors.lastname: Abasolo
authors.affiliation: CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebrón and Vall d'Hebrón Institut de Recerca, Universitat Autónoma de Barcelona , 08035 Barcelona, Spain.
authors.forename: Simó
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Depto. de Ingeniería, Área Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández , Carretera Alicante-Valencia km. 87, 03550 San Juan, Alicante, Spain.
authors.forename: Marival
authors.initials: M
authors.lastname: Bermejo
authors.affiliation: Instituto Mixto de Tecnología Química, Universidad Politécnica de Valencia-Consejo Superior de Investigaciones Científicas (UPV-CSIC) , Avd. de los Naranjos s/n, 46006 Valencia, Spain.
authors.forename: Avelino
authors.initials: A
authors.lastname: Corma
keywords: 9-substituted camptothecins; Lipophilic camptothecin; Tscherniac−Einhorn derivatives; oral administration