title: Synthesis and biological evaluation of new podophyllic aldehyde derivatives with cytotoxic and apoptosis-inducing activities.
abstract: Several series of nonlactonic podophyllic aldehyde analogues were prepared and evaluated against several human tumor cell lines. They had different combinations of aldehyde, imine, amine, ester, and amide functions at C-9 and C-9' of the cyclolignan skeleton. All the compounds synthesized showed cytotoxicity levels in the microM range and below. Within the new series tested, compounds having an aldehyde or imine at C-9 and an ester at C-9' were the most potent, with GI(50) values in the nM range, some of them being several times more potent against HT-29 and A-549 carcinoma than against MB-231 melanoma cells. Cell cycle studies and analysis of the microtubule-disrupting capacity have demonstrated the existence of two different mechanisms of cell death induction for compounds with closely related structures.
authors.affiliation: Departamento de Quimica Farmaceutica, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, E-37007 Salamanca, Spain. macg@usal.es
authors.forename: Ma Angeles
authors.initials: MA
authors.lastname: Castro
authors.forename: José Ma Miguel
authors.initials: JM
authors.lastname: del Corral
authors.forename: Pablo A
authors.initials: PA
authors.lastname: García
authors.forename: Ma Victoria
authors.initials: MV
authors.lastname: Rojo
authors.forename: Janis
authors.initials: J
authors.lastname: de la Iglesia-Vicente
authors.forename: Faustino
authors.initials: F
authors.lastname: Mollinedo
authors.forename: Carmen
authors.initials: C
authors.lastname: Cuevas
authors.forename: Arturo
authors.initials: A
authors.lastname: San Feliciano
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000188:drug therapy; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000447:Aldehydes; D000970:Antineoplastic Agents; C507546:podophyllic acid; D011034:Podophyllotoxin