title: Synthesis and biological evaluation of isoprenylated coumarins as potential anti-pancreatic cancer agents.
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 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.
authors.affiliation: Department of Chemistry, Wellesley College, Wellesley, MA 02481, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jun
authors.affiliation: Department of Chemistry, Wellesley College, Wellesley, MA 02481, USA.
authors.forename: Alyssa F
authors.initials: AF
authors.lastname: Bacay
authors.affiliation: Department of Chemistry, Wellesley College, Wellesley, MA 02481, USA.
authors.forename: James
authors.initials: J
authors.lastname: Moyer
authors.affiliation: Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Webb
authors.affiliation: Department of Chemistry, Wellesley College, Wellesley, MA 02481, USA.
authors.forename: Dora
authors.initials: D
authors.lastname: Carrico-Moniz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000473:pathology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins
keywords: Coumarins; PANC-1; Pancreatic cancer; Preferential cytotoxicity; Structure–activity relationships