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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Cytotoxicity of 5H-Dibenzo[c,h][1,6]naphthyridin-6-ones and 6H-Indeno[1,2-c]isoquinolin-5,11-diones in Tumor Cells Sensitive and Resistant to Camptothecin Analogs

Author(s): Alexander L. Ruchelman, Sudhir K. Singh, Angela Liu, Nai Zhou, Leroy F. Liu and Edmond J. La Voie

Volume 1 , Issue 3 , 2004

Page: [198 - 202] Pages: 5

DOI: 10.2174/1570180043399064

Price: $65


Several 6H-indeno[1,2-c]isoquinolin-5,11-diones and 5H-dibenzo[c,h][1,6]naphthyridin-6-ones were synthesized and evaluated for their relative topoisomerase I-targeting activity and cytotoxicity. Comparative studies were performed in P388, RPMI8402, and U937 tumor cell lines, as well as their camptothecin-resistant variants, i.e. P388 / CPT45, CPT-K5, and U937 / CR, respectively. The relative cytotoxic activity of these compounds in cell lines known to overexpress efflux transporters that are associated with multidrug resistance or are known to be resistant to topoisomerase II-targeting agents was also determined. Our results suggest that some of these compounds are highly potent TOP1-specific poisons with cytotoxic activity rivaling that of camptothecin and different drug-resistant profiles.

Keywords: cytotoxicity, dibenzo[c,h][1,6]naphthyridines, indeno[1,2-c]isoquinolines, topoisomerase, multidrug resistance

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