2. Academic Validation
  3. A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability

A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability

  • Eur J Med Chem. 2014 Aug 18:83:366-73. doi: 10.1016/j.ejmech.2014.06.050.
Guillermo Rodríguez-Berna 1,  Víctor Mangas-Sanjuán 2,  Marta Gonzalez-Alvarez 2,  Isabel Gonzalez-Alvarez 2,  José Luis García-Giménez 3,  María José Díaz Cabañas 4,  Marival Bermejo 2,  Avelino Corma 4
Affiliations

Affiliations

  • 1 Instituto de Tecnología Química, Universidad Politécnica de Valencia-Consejo, Superior de Investigaciones Científicas (UPV-CSIC), Avd. de los Naranjos s/n, 46022, Valencia, Spain. Electronic address: grodrig@itq.upv.es.
  • 2 Depto. de Ingeniería, Area Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández, Carretera Alicante-Valencia km. 87, 03550, San Juan, Alicante, Spain.
  • 3 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Depto. de Fisiología, Universidad de Valencia, Instituto de Investigación Sanitaria INCLIVA, Avd. Blasco Ibañez, 15, 46010, Valencia, Spain.
  • 4 Instituto de Tecnología Química, Universidad Politécnica de Valencia-Consejo, Superior de Investigaciones Científicas (UPV-CSIC), Avd. de los Naranjos s/n, 46022, Valencia, Spain.
PMID: 24980118 DOI: 10.1016/j.ejmech.2014.06.050
Abstract

Oral administration of camptothecin (CPT) derivatives and Other antitumoral agents is being actively developed in order to improve the quality of life of patients with Cancer. Though several lipophilic derivatives of CPT have shown interesting oral bioavailability in preclinical and clinical studies, only Topotecan has been approved for this route of administration. Semisynthesis, antitumor activity, biological inhibition mechanism, and in situ intestinal permeability of 9, 10-[1,3]-Dioxinocamptothecin (CDiox), an unexplored CPT derivative, have been studied in this paper. The hexacyclic analog was as effective as Topotecan and CPT in different tumor cell lines, showing an expected similar Apoptosis cell mechanism and high ability to inhibit DNA synthesis in HeLa, Caco-2, A375 and MDA-MB-231 cell lines. Furthermore, in vitro and in situ pharmacokinetics transport values obtained for CDiox displayed more favorable absorption profile than CPT and Topotecan.

Keywords

Antitumor; Camptothecin; Dioxinocamptothecin; Oral; Permeability; Transport.

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