title: A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability.
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.
authors: 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.
authors: Guillermo
authors: G
authors: Rodríguez-Berna
authors: Depto. de Ingeniería, Area Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández, Carretera Alicante-Valencia km. 87, 03550, San Juan, Alicante, Spain.
authors: Víctor
authors: V
authors: Mangas-Sanjuán
authors: Depto. de Ingeniería, Area Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández, Carretera Alicante-Valencia km. 87, 03550, San Juan, Alicante, Spain.
authors: Marta
authors: M
authors: Gonzalez-Alvarez
authors: Depto. de Ingeniería, Area Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández, Carretera Alicante-Valencia km. 87, 03550, San Juan, Alicante, Spain.
authors: Isabel
authors: I
authors: Gonzalez-Alvarez
authors: 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.
authors: José Luis
authors: JL
authors: García-Giménez
authors: Instituto de Tecnología Química, Universidad Politécnica de Valencia-Consejo, Superior de Investigaciones Científicas (UPV-CSIC), Avd. de los Naranjos s/n, 46022, Valencia, Spain.
authors: María José
authors: MJ
authors: Díaz Cabañas
authors: Depto. de Ingeniería, Area Farmacia y Tecnología Farmacéutica, Universidad Miguel Hernández, Carretera Alicante-Valencia km. 87, 03550, San Juan, Alicante, Spain.
authors: Marival
authors: M
authors: Bermejo
authors: Instituto de Tecnología Química, Universidad Politécnica de Valencia-Consejo, Superior de Investigaciones Científicas (UPV-CSIC), Avd. de los Naranjos s/n, 46022, Valencia, Spain.
authors: Avelino
authors: A
authors: Corma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001692:Biological Transport; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D010539:Permeability; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D002166:Camptothecin
keywords: Antitumor; Camptothecin; Dioxinocamptothecin; Oral; Permeability; Transport