title: Synthesis and structure-activity relationships of new benzodioxinic lactones as potential anticancer drugs.
abstract: A set of disubstituted tetracyclic lactones has been synthesized and tested for potential antitumor activity. Several of them possess a noticeable cytotoxicity against L1210 and HT-29 colon cells in vitro. Relationships between chain nature and biological properties were sought. Lactones with a pentyl or hexyl substituent at C-11 are the most active ones. The introduction of a functional group at the side chain of C-11 modified the potency; carboxylic acid and primary amine decreased the cytotoxicity, whereas a cyano group increased the activity. An extensive structure-activity relationship study of these derivatives, including carbon homologues and bioisosteres has been performed. The synthesis and cytotoxicity of these compounds are discussed. Two lactones are recognized as potential lead compounds.
authors.affiliation: Laboratori de Química Farmacèutica, Unitat Associada al CSIC, Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, 08028-Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Romero
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Daniel-Henry
authors.initials: DH
authors.lastname: Caignard
authors.forename: Ghanen
authors.initials: G
authors.lastname: Atassi
authors.forename: Xavier
authors.initials: X
authors.lastname: Solans
authors.forename: Pere
authors.initials: P
authors.lastname: Constans
authors.forename: Christian
authors.initials: C
authors.lastname: Bailly
authors.forename: Maria Dolors
authors.initials: MD
authors.lastname: Pujol
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004147:Dioxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D004147:Dioxins; D007546:Isoquinolines; D007783:Lactones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors