Curcumin-1,2,3-Triazole conjugation for targeting the cancer apoptosis machinery

Francesca Seghetti, Rita Maria Concetta Di Martino, Elena Catanzaro, Alessandra Bisi, Silvia Gobbi, Angela Rampa, Barbara Canonico, Mariele Montanari, Dmitri V. Krysko, Stefano Papa, Carmela Fimognari, Federica Belluti

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

The burden of neoplastic diseasesis widely recognized as a severe cause ofmortality. The clinical inadequacy of most anticancer therapeutics urgently prompted intense drug discovery efforts toward the identification of new chemical entities endowed with a potent and safe antitumor profile. In this scenario, targeting cancer cells apoptosis machinery has emerged as a relevant strategy, useful for tackling the emergence of drug resistance. On this basis, a small library of naturally inspired hybrid molecules was obtained by combining, through a click chemistry approach, "privileged" synthons such as curcumin scaffold and 1,2,3-triazole building block. Compound 1, bearing a para-fluoro phenyl moiety, showed low-micromolar potency against T acute lymphoblastic leukemia cell growth. More in-depth biologic studies demonstrated, for this analog, cell death-inducing properties associated with its capability to simultaneously activate both the receptor and the mitochondrial apoptosis cascades. This peculiar behavior offers promises for achieving an expanded anticancer effect, namely intense cytotoxic response coupled with reduced predisposition of chemoresistance insurgence. Altogether, this study allowed the identification of compound 1 as a lead compound worth to be progressed as an anticancer drug candidate.

Lingua originaleInglese
Numero di articolo3066
RivistaMolecules
Volume25
Numero di pubblicazione13
DOI
Stato di pubblicazionePubblicato - lug 2020
Pubblicato esternamente

Fingerprint

Entra nei temi di ricerca di 'Curcumin-1,2,3-Triazole conjugation for targeting the cancer apoptosis machinery'. Insieme formano una fingerprint unica.

Cita questo