Mannich Curcuminoids as Potent Anticancer Agents.
Márió GyurisLászló HacklerLajos I NagyRóbert AlföldiEszter RédeiAnnamária MartonTibor VellaiNóra FaragóBéla ÓzsváriAnasztázia HetényiGábor K TóthPéter SiposIván KanizsaiLászló G PuskásPublished in: Archiv der Pharmazie (2017)
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.
Keyphrases
- structure activity relationship
- signaling pathway
- induced apoptosis
- oxidative stress
- cell cycle arrest
- endoplasmic reticulum stress
- cell death
- drug delivery
- molecular docking
- rheumatoid arthritis
- high resolution
- high glucose
- pi k akt
- diabetic rats
- high throughput
- stem cells
- case control
- drug induced
- endothelial cells
- climate change
- inflammatory response
- amino acid
- molecular dynamics simulations
- mass spectrometry
- stress induced
- single cell