Synthesis and biological evaluation of isoprenylated coumarins as potential anti-pancreatic cancer agents

被引：32

作者：

Jun, Maria ^{[1
]}

Bacay, Alyssa F. ^{[1
]}

Moyer, James ^{[1
]}

Webb, Andrew ^{[2
]}

Carrico-Moniz, Dora ^{[1
]}

机构：

[1] Wellesley Coll, Dept Chem, Wellesley, MA 02481 USA

[2] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02481 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 19期

关键词：

Coumarins; Preferential cytotoxicity; Pancreatic cancer; PANC-1; Structure-activity relationships; NUTRIENT DEPRIVATION; CELLS; TOLERANCE; GEMCITABINE; ELIMINATE;

D O I：

10.1016/j.bmcl.2014.08.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of isoprenylated coumarins has been designed, synthesized, and evaluated against human pancreatic adenocarcinoma cell line PANC-1 under nutrient-rich and nutrient-deprived conditions. The compounds described investigate the effect of isoprenyl chain length and positioning on cell growth inhibition. The majority of these compounds displayed cytotoxicity against PANC-1 cells selectively in the absence of essential amino acids, glucose, and serum, and showed no cytotoxicity under nutrient-rich conditions. In this study, compound 6 exhibited the highest cytotoxic activity with an LC50 value of 4 mu M and induced apoptosis-like morphological changes in PANC-1 cells after a 24-h incubation. The evaluated structure-activity relationships show that substitution at the 6-position and the presence of a farnesyl isoprenyl tail are important structural features for enhanced preferential cytotoxicity. These findings provide important information to designing other structural analogues for potential application as novel pancreatic antitumor agents. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：4654 / 4658

页数：5

共 17 条

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