Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery

Abstract

<jats:p>The burden of neoplastic diseases is widely recognized as a severe cause of mortality. 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.</jats:p>

Modulation of Amyloid β-Induced Microglia Activation and Neuronal Cell Death by Curcumin and Analogues

“…In this scenario, a number of properly modified curcumin derivatives endowed with an improved biological profile have been developed, confirming the significant potential of the curcuminoid scaffold as previously documented [27,34]. Particularly evident outcomes have been obtained in the anticancer and anti-neurodegenerative therapeutic areas [30,[35][36][37].…”

1,2,3‐Triazole hybrids as anticancer agents: A review

“…Conjugate 20 also activated apoptosis signaling pathways, potentially inducing optimal activation of the apoptotic machinery. [40] Eugenol- MCF-7 cells compared to doxorubicin (IC 50 value of 5.46 μM). [41] Novel xanthone-1,2,3-triazole derivative 24 was found to be a potent cytotoxic agent, with an IC 50 value of 32.4 μM against A549 cancer cells, which significantly increased the expression of caspase 3, Bax, JNK, and p53, causing cell cycle arrest and apoptosis in cancer cells.…”

Molecular Engineering of Curcumin, an Active Constituent of Curcuma longa L. (Turmeric) of the Family Zingiberaceae with Improved Antiproliferative Activity

“…In most of the cases, the chemical modifications of diketonic function of curcumin into pyrazole and primidinone analogues were found to be promising, whereas chemical modification of diketonic function that resulted in bigenelli-type curcumin compounds were found to be least significant [ 18 , 19 , 20 , 54 ]. Curcumin analogues previously reported in the literature demonstrated cytotoxicity on the CCGF-CEM cell line with IC 50 values ranging from 3.13 to 93.40 µM, whereas compounds ( 3b , c ) were found to be much more potent than the reported curcumin analogues [ 55 ].…”