Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity

doi:10.1016/j.bmcl.2004.08.070

Bioorganic & Medicinal Chemistry Letters

Volume 14, Issue 22, 15 November 2004, Pages 5585-5589

https://doi.org/10.1016/j.bmcl.2004.08.070 Get rights and content

Abstract

The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1, prompted studies on similarly substituted benzo[i]phenanthridine-12-carboxylic ester and amide derivatives. These studies were extended to include 6-substituted 8,9-dimethoxy-2,3-methylenedioxy-dibenzo[c,h][2,6]naphthyridin-5-ones, which represent reversed lactam analogues of 1. Several of these analogues retained the potent TOP1-targeting activity and cytotoxicity observed for ARC-111.

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Acknowledgements

This study was supported by Grant CA098127 (E.J.L.) and Grant CA39662 (L.F.L.) and Grant CA077433 (L.F.L.) from the National Cancer Institute.

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Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity

Abstract

Graphical abstract

Section snippets

Acknowledgements

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Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem.

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Annu. Rev. Biochem.

Annu. Rev. Biochem.