Multitarget-directed drug design strategy: a novel molecule designed to block epidermal growth factor receptor (EGFR) and to exert proapoptotic effects.
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.
Antonello
Alessandra
A
Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Tarozzi
Andrea
A
Morroni
Fabiana
F
Cavalli
Andrea
A
Rosini
Michela
M
Hrelia
Patrizia
P
Bolognesi
Maria Laura
ML
Melchiorre
Carlo
C
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
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors