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

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Abstract

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 μM 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.

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Acknowledgments

This work was supported in part by a Faculty Award Grant from Wellesley College. M.J. and A.B. were supported by a Roberta Day Staley and Karl A. Staley Funds for Cancer-Related Research award from Wellesley College. M.J. was also supported by a Jean Dreyfus Boissevain Lectureship for Undergraduate Institutions award.

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Maria Jun and Alyssa F. Bacay contributed equally to this work.

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