title: Lignopurines: a new family of hybrids between cyclolignans and purines. Synthesis and biological evaluation.
abstract: A new family of hybrids between cyclolignans related to podophyllic aldehyde, a non-lactonic cyclolignan, and purines were prepared and evaluated against several human tumour cell lines. Both fragments, cyclolignan and purine, were linked through aliphatic and aromatic chains. The influence on the cytotoxicity of the purine substitution and the nature of the linker is analyzed. The new family was slightly less cytotoxic than the parent podophyllic aldehyde, although the selectivity is maintained or even improved and among the linkers used, the presence of an aromatic ring gave the most potent and selective derivatives within the new series tested. Cell cycle and confocal studies demonstrate that these derivatives interfere with the tubulin polymerization and arrest cells at the G(2)/M phase, in the same way than the parent compounds podophyllotoxin and podophyllic aldehyde do.
authors.affiliation: Departamento de Química Farmacéutica, Facultad de Farmacia, CIETUS-IBSAL, Campus Miguel de Unamuno, Universidad de Salamanca, E-37007 Salamanca, Spain. macg@usal.es
authors.forename: Ma Ángeles
authors.initials: MÁ
authors.lastname: Castro
authors.forename: José Ma
authors.initials: JM
authors.lastname: Miguel del Corral
authors.forename: Pablo A
authors.initials: PA
authors.lastname: García
authors.forename: Ma Victoria
authors.initials: MV
authors.lastname: Rojo
authors.forename: Ana C
authors.initials: AC
authors.lastname: Bento
authors.forename: Faustino
authors.initials: F
authors.lastname: Mollinedo
authors.forename: Andrés M
authors.initials: AM
authors.lastname: Francesch
authors.forename: Arturo
authors.initials: A
authors.lastname: San Feliciano
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D017705:Lignans; D011687:Purines