Combining a Solution-Phase Derived Library with In-Situ Cellular Bioassay: Prompt Screening of Amide-Forming Minilibraries Using MTT Assay

被引：14

作者：

Chiang, Li-Wu ^{[1
]}

Pei, Kai ^{[1
]}

Chen, Shao-Wei ^{[1
]}

Huang, Ho-Lien ^{[1
]}

Lin, Kun-Ju ^{[3
]}

Yen, Tzu-Chen ^{[3
]}

Yu, Chung-Shan ^{[1
,2
]}

机构：

[1] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu 30043, Taiwan

[2] Natl Tsing Hua Univ, Inst Nucl Engn & Sci, Hsinchu 30043, Taiwan

[3] Chang Gung Mem Hosp, Dept Nucl Med, Tao Yuan 33305, Taiwan

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 2009年 / 57卷 / 07期

关键词：

amide; assay; solution phase; in situ; library; molecular docking; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GLUTATHIONE-S-TRANSFERASE; ETHACRYNIC-ACID; INHIBITOR; POTENT; CYCLOOXYGENASE-2; SPHINGOLIPIDS; EXPRESSION; DISCOVERY; APOPTOSIS;

D O I：

10.1248/cpb.57.714

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We constructed a minilibrary using a solution-phase synthesis through coupling of three core amino compounds (5'-amino-5'-deoxy uridine, 5'-amino-2',5'-di-deoxy arabinosyl uridine, and butan-l-amine) with 30 carboxylic acids via amide bond formation. The simplified structural core compound butan-l-amine was selectively coupled with 9 carboxylic acids as control. 3-(4,5-Dimethyl-2-thiazolyi)-2,5-diphenyl-2H-tetrazolium bromide assay of the crude mixtures showed that analogues derived from fenbufen, butylfenbufen C15; ethacrynic acid, butyl ethacrynic amide C18; and sphingosines, Sph-1, Sph-2 and U27 had an increased cytotoxicity against MCF-7 cells as well as A549 cells. Structural elucidation with molecular docking suggested that cytotoxicity of these compounds is mainly due to the inhibition of enzymes regulating cellular apoptosis.

引用

页码：714 / 718

页数：5

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