Mannich Curcuminoids as Potent Anticancer Agents

被引：26

作者：

Gyuris, Mario ^{[1
]}

Hackler, Laszlo, Jr. ^{[1
]}

Nagy, Lajos I. ^{[1
]}

Alfoldi, Robert ^{[1
]}

Redei, Eszter ^{[1
]}

Marton, Annamaria ^{[2
]}

Vellai, Tibor ^{[3
]}

Farago, Nora ^{[1
]}

Ozsvari, Bela ^{[1
]}

Hetenyi, Anasztazia ^{[4
]}

Toth, Gabor K. ^{[4
]}

Sipos, Peter ^{[5
]}

Kanizsai, Ivan ^{[1
]}

Puskas, Laszlo G. ^{[1
]}

机构：

[1] AVIDIN Ltd, Kikoto Sor 11, H-6726 Szeged, Hungary

[2] Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, Szeged, Hungary

[3] Univ Szeged, Dept Med Chem, Fac Gen Med, Szeged, Hungary

[4] Eotvos Lorand Univ, Dept Genet, Budapest, Hungary

[5] Univ Szeged, Dept Pharmaceut Technol, Fac Pharm, Szeged, Hungary

来源：

ARCHIV DER PHARMAZIE | 2017年 / 350卷 / 07期

关键词：

Anticancer; Autophagy; Curcuminoids; Mannich; NF-kappa B inhibition; LUNG-CANCER CELLS; NF-KAPPA-B; IN-VITRO; DERIVATIVE HYDRAZINOBENZOYLCURCUMIN; BIOLOGICAL EVALUATION; DOWN-REGULATION; ANALOGS; APOPTOSIS; AUTOPHAGY; VIVO;

D O I：

10.1002/ardp.201700005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 TNF alpha-induced NF-kappa B 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.

引用

页数：22

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