Tricyclic Benzimidazoles as Potent Poly(ADP-ribose) Polymerase-1 Inhibitors

Donald J. Skalitzky, Joseph Marakovits, Karen A. Maegley, Anne Ekker, Xiaohong Yu, Zdeněk Hostomský, Stephen E. Webber, Brian Eastman, Robert J. Almassy, Jianke Li,

Journal of Medicinal Chemistry · 2002 · 152 citations · 4 references

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Abstract

Novel tricyclic benzimidazole carboxamide poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been synthesized. Several compounds were found to be powerful chemopotentiators of temozolomide and topotecan in both A549 and LoVo cell lines. In vitro inhibition of PARP-1 was confirmed by direct measurement of NAD+ depletion and ADP-ribose polymer formation caused by chemically induced DNA damage.

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