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 4μM 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.
Keywords: Coumarins; PANC-1; Pancreatic cancer; Preferential cytotoxicity; Structure–activity relationships.
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