Natural products that inhibit cell cycle progression show promise as anticancer agents and chemical probes. In our research on biologically active natural products that affect cell cycle progression of HeLa/fluorescent ubiquitination-based cell cycle indicator (Fucci)2 cells, the extract of the marine sponge Neopetrosia chaliniformis was revealed to inhibit cell proliferation. Purification of the extract afforded four new pyridine alkaloids, neopetrosidines A-D (1-4). Their structures were elucidated by the interpretation of spectroscopic data and chemical degradation. Compounds 1-4 were found to inhibit cell proliferation of HeLa/Fucci2 cells, and time-lapse imaging showed that 1 exerts its effect by increasing the duration of the cell cycle. Furthermore, we show that 1 perturbs bioenergetics to exhibit a cytostatic effect by reducing the mitochondrial membrane potential.
Keywords: Cell cycle elongation activity; HeLa/Fucci2 cell; Marine sponge; Neopetrosia chaliniformis; Pyridine alkaloid.
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