TY - JOUR
T1 - 6-Substituted 6H-dibenzo[c,h][2,6]naphthyridin-5-ones
T2 - Reversed lactam analogues of ARC-111 with potent topoisomerase I-targeting activity and cytotoxicity
AU - Zhu, Shejin
AU - Ruchelman, Alexander L.
AU - Zhou, Nai
AU - Liu, Angela
AU - Liu, Leroy F.
AU - LaVoie, Edmond J.
N1 - Funding Information:
This study was supported by Grant CA098127 (E.J.L.), Grant CA39662 (L.F.L.), and Grant CA077433 (L.F.L.) from the National Cancer Institute.
PY - 2006/5/1
Y1 - 2006/5/1
N2 - 6-Substituted 8,9-dimethoxy-2,3-methylenedioxy-6H-dibenzo[c,h][2,6] naphthyridin-5-ones were synthesized and evaluated for topoisomerase I-targeting activity and cytotoxicity. Several of these reversed lactam analogues of ARC-111 exhibited exceptional cytotoxicity with IC50 values ranging from 0.5 to 3.0 nM. In contrast to topotecan, no resistance was observed with several of these reversed lactam analogues in tumor cell lines that overexpressed the efflux transporters MDR1 or BCRP.
AB - 6-Substituted 8,9-dimethoxy-2,3-methylenedioxy-6H-dibenzo[c,h][2,6] naphthyridin-5-ones were synthesized and evaluated for topoisomerase I-targeting activity and cytotoxicity. Several of these reversed lactam analogues of ARC-111 exhibited exceptional cytotoxicity with IC50 values ranging from 0.5 to 3.0 nM. In contrast to topotecan, no resistance was observed with several of these reversed lactam analogues in tumor cell lines that overexpressed the efflux transporters MDR1 or BCRP.
KW - Antitumor
KW - Cytotoxic
KW - Dibenzo[c,h][2,6]naphthyridin-5-ones
KW - Topoisomerase I
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U2 - 10.1016/j.bmc.2005.12.028
DO - 10.1016/j.bmc.2005.12.028
M3 - Article
C2 - 16412652
AN - SCOPUS:33644987261
VL - 14
SP - 3131
EP - 3143
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 9
ER -