6533b7d2fe1ef96bd125f7fc
RESEARCH PRODUCT
A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability.
Victor Mangas-sanjuanMarta González-álvarezMaria Jose Diaz CabañasGuillermo Rodríguez-bernaAvelino CormaIsabel González-álvarezMarival BermejoJosé Luis García-giménezsubject
Oralendocrine system diseasesCellDioxinocamptothecinTransportAntineoplastic AgentsChemistry Techniques SyntheticPharmacologyPermeabilityHeLaQUIMICA ORGANICAPharmacokineticsOral administrationCell Line TumorDrug DiscoverymedicineAnimalsHumansheterocyclic compoundsIntestinal MucosaneoplasmsPharmacologybiologyChemistryOrganic ChemistryBiological TransportGeneral MedicineAntitumorbiology.organism_classificationSemisynthesisIn vitroRatsmedicine.anatomical_structureTopotecanCamptothecinCamptothecinmedicine.drugdescription
Oral administration of camptothecin (Cm) 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. (C) 2014 Elsevier Masson SAS. All rights reserved.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-03-26 | European journal of medicinal chemistry |