1-(3-Aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones: A novel group of tumour-selective cytotoxins

被引：34

作者：

Bilginer, Sinan ^{[1
]}

Gul, Halise Inci ^{[1
]}

Mete, Ebru ^{[2
]}

Das, Umashankar ^{[3
]}

Sakagami, Hiroshi ^{[4
]}

Umemura, Naoki ^{[4
]}

Dimmock, Jonathan Richard ^{[3
]}

机构：

[1] Ataturk Univ, Dept Pharmaceut Chem, Fac Pharm, Erzurum, Turkey

[2] Ataturk Univ, Fac Sci, Dept Chem, Erzurum, Turkey

[3] Univ Saskatchewan, Coll Pharm & Nutr, Drug Design & Discovery Res Grp, Saskatoon, SK, Canada

[4] Meikai Univ, Sch Dent, Div Pharmacol, Sakado, Saitama 3500283, Japan

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2013年 / 28卷 / 05期

关键词：

Mannich bases; azachalcones; cytotoxicity; molecular modelling; PARP1; MANNICH-BASES; CHALCONES; TOXICITY;

D O I：

10.3109/14756366.2012.700927

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Two series of 1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones, designed as novel cytotoxins, were synthesized. The compounds had low CC50 values in the micromolar range against HL-60 promyelocytic leukemic cells and HSC-2, HSC-3 and HSC-4 oral squamous cell carcinomas. The CC 50 values of these compounds were higher towards non-malignant HGF (gingival fibroblasts), HPC (pulp cells), and HPLF (periodontal ligament fibroblasts) cells, which reveals the tumour-selectivity of these enones. A representative compound 4c caused cleavage of PARP1 in HSC-2 cells but not in HGF cells, which may be a contributing factor to the tumour-selectivity.

引用

页码：974 / 980

页数：7

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