Mannich Curcuminoids as Potent Anticancer Agents

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. Novel Mannich curcuminoids were synthesized and their antiproliferative activities were tested against lung adenocarcinoma cells. Structure–activity relationships and the background of TNFα‐induced NF‐κB inhibition and autophagy induction were established. The lead compound N‐((E)‐5‐(3‐hydroxyphenyl)‐2‐((E)‐3‐(3‐hydroxyphenyl)acryloyl)‐3‐oxo‐1‐phenylpent‐4‐en‐1‐yl)acrylamide 44 led to significant tumour size reduction in the A549 xenograft model.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research