Mannich Curcuminoids as Potent Anticancer Agents

Abstract

A series of novel curcuminoids were synthesised for the first time via a Mannich-3CR/organocatalysed Claisen-Schmidt condensation sequence. Structure-activity relationship (SAR) studies were performed by applying viability assays and holographic microscopic imaging to these curcumin analogues for anti-proliferative activity against A549 and H1975 lung adenocarcinoma cells. The TNFα-induced NF-κB inhibition and autophagy induction effects correlated strongly with the cytotoxic potential of the analogues. Significant inhibition of tumour growth was observed when the most potent analogue 44 was added in liposomes at one-sixth of the maximally tolerated dose in the A549 xenograft model. The novel spectrum of activity of these Mannich curcuminoids warrants further preclinical investigations.

Achiral Mannich-Base Curcumin Analogs Induce Unfolded Protein Response and Mitochondrial Membrane Depolarization in PANC-1 Cells

“…Recently, we have reported the potent cytotoxic activity of racemic Mannich-type curcumin analogs [ 15 , 16 , 17 ]. Here, we report the cytotoxic activity of the achiral curcumin analog library (C500 series) ( Figure 1 and Figure S1 ).…”

Identification of compound CA-5f as a novel late-stage autophagy inhibitor with potent anti-tumor effect against non-small cell lung cancer

“…Curcumin is a natural polyphenol derived from the herb Curcuma longa that suppresses the growth of various types of cancer cells by regulating autophagy [20][21][22][23]. Although poor bioavailability in vivo limits its clinical applications, curcumin remains a good lead compound for further structure modification, as an increasing number of curcumin analogs or derivatives have been reported to induce autophagy and kill cancer cells [24][25][26]. Several studies have demonstrated that curcumin is capable of inducing autophagy in different lines of human tumor and normal cells [22,23,[27][28][29].…”

Synthesis and biological evaluation of 4,5,6,7‐tetrahydrothieno[2,3‐c]pyridine–based β‐aminonitriles and their derivatives: β‐amino carboxamides, (thio)ureas, and tetracycles

“…To visualize the effects of treatments, holographic microscopic analysis was performed. Using this technology, morphological parameters of treated cells such as area, thickness, and volume can be followed in a label‐free way . A549 human lung adenocarcinoma cells were incubated with two concentrations of the selected analogues.…”