title: Multitarget-directed drug design strategy: a novel molecule designed to block epidermal growth factor receptor (EGFR) and to exert proapoptotic effects.
abstract: The multifactorial mechanistic nature of cancer calls for the development of multifunctional therapeutic tools, i.e., single compounds able to interact with multiple altered pathogenetic pathways. Following this rationale, we designed compounds able to irreversibly block epidermal growth factor receptor (EGFR), and to induce apoptosis in tumor cell lines. The novel molecules were synthesized by combining the structural features of the EGFR inhibitor PD153035 (1) and lipoic acid, which among other therapeutic effects triggers apoptosis in human cancer cells.
authors.affiliation: Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Antonello
authors.forename: Andrea
authors.initials: A
authors.lastname: Tarozzi
authors.forename: Fabiana
authors.initials: F
authors.lastname: Morroni
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Michela
authors.initials: M
authors.lastname: Rosini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bolognesi
authors.forename: Carlo
authors.initials: C
authors.lastname: Melchiorre
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors