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Bioorg Med Chem Lett ; 40: 127967, 2021 05 15.
Article in English | MEDLINE | ID: mdl-33753259

ABSTRACT

An ethanolic extract of Derris scandens flowers showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived condition, with a PC50 value of 0.7 µg/mL. Phytochemical investigation of this active extract led to the isolation of four prenylated isoflavones (1-4) including a new compound named 4'-O-methylgrynullarin (1). The structure elucidation of the new compound was achieved by HRFABMS and NMR spectroscopic analysis. The isolated compounds exhibited potent anti-austerity activity against four different human pancreatic cancer cell lines under nutrient-deprived conditions. The new compound 4'-O-methylgrynullarin (1) was also found to inhibit PANC-1 cell migration and colony formation under nutrient-rich condition. Mechanistically, compound 1 inhibited key survival proteins in the Akt/mTOR signaling pathway. Therefore, 4'-O-methylgrynullarin (1) can be considered as a potential lead compound for the anticancer drug development based on the anti-austerity strategy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cell Death/drug effects , Hemiterpenes/pharmacology , Isoflavones/pharmacology , Pancreatic Neoplasms/drug therapy , Signal Transduction/drug effects , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Movement/drug effects , Derris/chemistry , Drug Screening Assays, Antitumor , Flowers/chemistry , Hemiterpenes/chemical synthesis , Hemiterpenes/isolation & purification , Humans , Isoflavones/chemistry , Isoflavones/isolation & purification , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism
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