Droserone and dioncoquinone B, and related naphthoquinones as potent antiausterity agents against human PANC-1 pancreatic cancer cells

Results in Chemistry, Год журнала: 2024, Номер 7, С. 101352 - 101352

Опубликована: Янв. 1, 2024

Pancreatic cancer is a highly aggressive disease with poor prognosis. Its tumor microenvironment characterized by severe nutrient deprivation and hypoxia, leading to the activation of adaptive pathways that allow cells survive thrive under these harsh conditions. This makes conventional therapies less effective, highlighting urgent need for novel treatment strategies. Naphthoquinones have recently emerged as promising anti-austerity agents, demonstrating preferential cytotoxicity against pancreatic in nutrient-deprived medium (NDM). To further explore their potential, we investigated structure–activity relationships mechanism action library 28 natural synthetic naphthoquinones. Our results reveal significant influence functional groups at positions C-2, C-3, C-5, C-6 on anticancer activity. Strong electron-donating substituents C-3 decreased activity, while electron-withdrawing H-bond acceptors (without donor activity) increased potency. The naphthoate esters 4 5 exhibited strongest activity PANC-1 cells, PC50 values 0.87 0.42 μM, respectively. These compounds significantly altered cell morphology, induced apoptosis, inhibited colony formation. Further investigation revealed compound downregulated expression Akt p-Akt(S473) proteins, suggesting its might involve suppression signaling pathway. findings demonstrate immense potential naphthoquinones agents targeting austerity-adapted cells. development holds treating this devastating disease.

Язык: Английский

Structural variety and pharmacological potential of naphthylisoquinoline alkaloids

˜The œAlkaloids. Chemistry and biology/˜The œalkaloids. Chemistry and biology, Год журнала: 2024, Номер unknown, С. 1 - 410

Опубликована: Янв. 1, 2024

Язык: Английский