Add time:07/24/2019         Source:sciencedirect.com

Topsentin, a bis(indolyl)imidazole marine natural product, inhibited the proliferation of cultured human and murine tumor cells at micromolar concentrations (ic50 values ranged from 4 to 40 μM) and was active against in vivo P388 leukemia (%TC = 137, 150 mg/kg, QD1-5) and B16 melanoma (%TC = 144, 37.5 mg/kg, QD1-9) tumors. Effects of 30 μM topsentin (1-hr exposures) on incorporation of radiolabeled precursors by P388 cells indicated inhibition of DNA synthesis (91%) and to a lesser extent RNA synthesis (57%), whereas synthesis of protein was unaffected (0%). Fluorescence spectral changes and competitive binding experiments with ethidium bromide indicated that topsentin interacted with DNA. No evidence for intercalation was observed in DNA unwinding studies, but competitive binding experiments with Hoechst 33342 and CC-1065 indicated that topsentin bound to DNA in the minor groove.

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