2. Academic Validation
  3. Semisynthesis, cytotoxic activity, and oral availability of new lipophilic 9-substituted camptothecin derivatives

Semisynthesis, cytotoxic activity, and oral availability of new lipophilic 9-substituted camptothecin derivatives

  • ACS Med Chem Lett. 2013 May 28;4(7):651-5. doi: 10.1021/ml400125z.
Guillermo Rodriguez-Berna 1,  Maria Jose Díaz Cabañas 1,  Victor Mangas-Sanjuán 2,  Marta Gonzalez-Alvarez 2,  Isabel Gonzalez-Alvarez 2,  Ibane Abasolo 3,  Simó Schwartz Jr 3,  Marival Bermejo 2,  Avelino Corma 1
Affiliations

Affiliations

  • 1 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.
  • 2 Depto. de Ingeniería, Área Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández , Carretera Alicante-Valencia km. 87, 03550 San Juan, Alicante, Spain.
  • 3 CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebrón and Vall d'Hebrón Institut de Recerca, Universitat Autónoma de Barcelona , 08035 Barcelona, Spain.
PMID: 24900725 DOI: 10.1021/ml400125z
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.

Keywords

9-substituted camptothecins; Lipophilic camptothecin; Tscherniac−Einhorn derivatives; oral administration.

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