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.

Tarozzi, A., Marchetti, C., Nicolini, B., D'Amico, M., Ticchi, N., Pruccoli, L., et al. (2016). Combined inhibition of the EGFR/AKT pathways by a novel conjugate of quinazoline with isothiocyanate. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 117, 283-291 [10.1016/j.ejmech.2016.04.002].

Combined inhibition of the EGFR/AKT pathways by a novel conjugate of quinazoline with isothiocyanate.

TAROZZI, ANDREA;MARCHETTI, CHIARA;NICOLINI, BENEDETTA;D'AMICO, MASSIMO;TICCHI, NICOLE;PRUCCOLI, LETIZIA;TUMIATTI, VINCENZO;SIMONI, ELENA;MILELLI, ANDREA;MINARINI, ANNA
2016

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.
2016
Tarozzi, A., Marchetti, C., Nicolini, B., D'Amico, M., Ticchi, N., Pruccoli, L., et al. (2016). Combined inhibition of the EGFR/AKT pathways by a novel conjugate of quinazoline with isothiocyanate. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 117, 283-291 [10.1016/j.ejmech.2016.04.002].
Tarozzi, A; Marchetti, C; Nicolini, B; D'Amico, M; Ticchi, N; Pruccoli, L; Tumiatti, V; Simoni, E; Lodola, A; Mor, M; Milelli, A; Minarini, A....espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/580075
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