A new anti-austerity agent, 4′-O-methylgrynullarin from Derris scandens induces PANC-1 human pancreatic cancer cell death under nutrition starvation via inhibition of Akt/mTOR pathway

• Published in: Bioorganic & medicinal chemistry letters Vol. 40; p. 127967
• Main Authors: Sun, Sijia, Dibwe, Dya Fita, Kim, Min Jo, Omar, Ashraf M., Phan, Nguyen Duy, Fujino, Haruka, Pongterdsak, Nusrin, Chaithatwatthana, Kritsaya, Phrutivorapongkul, Ampai, Awale, Suresh
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-05-2021
• Subjects: Anti-austerity agents; Derris scandens; PANC-1; Pancreatic cancer; Preferential cytotoxicity; Derris scandens; Preferential cytotoxicity; Anti-austerity agents; Pancreatic cancer; PANC-1
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.127967

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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.