Abstract:
:Epidermal growth factor receptor inhibitors (EGFR-TKIs) represent a class of compounds widely used in anticancer therapy. An increasing number of studies reports on combination therapies in which the block of the EGFR-TK activity is associated with inhibition of its downstream pathways, as PI3K-Akt. Sulforaphane targets the PI3K-Akt pathway whose dysregulation is implicated in many functions of cancer cells. According to these considerations, a series of multitarget molecules have been designed by combining key structural features derived from an EGFR-TKI, PD168393, and the isothiocyanate sulforaphane. Among the obtained molecules 1-6, compound 6 emerges as a promising lead compound able to exert antiproliferative and proapoptotic effects in A431 epithelial cancer cell line by covalently binding to EGFR-TK, and reducing the phosphorylation of Akt without affecting the total Akt levels.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Tarozzi A,Marchetti C,Nicolini B,D'Amico M,Ticchi N,Pruccoli L,Tumiatti V,Simoni E,Lodola A,Mor M,Milelli A,Minarini Adoi
10.1016/j.ejmech.2016.04.002subject
Has Abstractpub_date
2016-07-19 00:00:00pages
283-91eissn
0223-5234issn
1768-3254pii
S0223-5234(16)30274-4journal_volume
117pub_type
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