Gyuris Márió, Hackler László, Nagy Lajos I, Alföldi Róbert, Rédei Eszter, Marton Annamária, Vellai Tibor, Faragó Nóra, Ózsvári Béla, Hetényi Anasztázia, Tóth Gábor K, Sipos Péter, Kanizsai Iván, Puskás László G
AVIDIN Ltd., Szeged, Hungary.
Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
Arch Pharm (Weinheim). 2017 Jul;350(7). doi: 10.1002/ardp.201700005. Epub 2017 May 26.
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.
首次通过曼尼希-3组分反应/有机催化克莱森-施密特缩合序列合成了一系列新型姜黄素类化合物。通过对这些姜黄素类似物进行活力测定和全息显微成像，研究其对A549和H1975肺腺癌细胞的抗增殖活性，以进行构效关系（SAR）研究。TNFα诱导的NF-κB抑制和自噬诱导效应与类似物的细胞毒性潜力密切相关。在A549异种移植模型中，当以最大耐受剂量的六分之一将最有效的类似物44添加到脂质体中时，观察到肿瘤生长受到显著抑制。这些曼尼希姜黄素类化合物的新活性谱值得进一步进行临床前研究。
