TY - JOUR
T1 - 8,9-Methylenedioxybenzo[i]phenanthridines
T2 - Topoisomerase I-targeting activity and cytotoxicity
AU - Li, Dajie
AU - Zhao, Baoping
AU - Sim, Sai Peng
AU - Li, Tsai Kun
AU - Liu, Angela
AU - Liu, Leroy F.
AU - LaVoie, Edmond J.
N1 - Funding Information:
We are grateful to Washington University Resource for Biomedical and Bio-Organic Mass Spectrometry for providing mass spectral data and for the partial support of this facility by the National Institutes of Health (Grant No. P41RR0954). We thank Mr. Nai Zhou for performing the nucleosomal DNA fragmentation assays as an indicator of apoptosis. This study was supported by AVAX Technologies, Inc, (E.J.L.) and Grant CA39662 (L.F.L.) and Grant CA077433 (L.F.L.) from the National Cancer Institute.
PY - 2003/8/15
Y1 - 2003/8/15
N2 - Substituted benzo[i]phenanthridines that have incorporated within their structure an 8,9-methylenedioxy group can exhibit topoisomerase I-targeting activity. Structure-activity studies were performed to examine the influence of saturation at the 11,12-positions of several substituted 8,9-methylenedioxybenzo[i]phenanthridines. The activities of these dihydro analogues were compared to those of their unsaturated analogues. In addition, the influence of varying substituents at the 2- and 3-positions within the A-ring of these 8,9-methylenedioxybenzo[i]phenanthridines on their relative potency as topoisomerase I-targeting agents and cell proliferation as determined using the MTT assay was investigated. 2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine and its 11,12-dihydro derivative were among the more potent analogues evaluated with regard to topoisomerase I-targeting activity and cytotoxicity.
AB - Substituted benzo[i]phenanthridines that have incorporated within their structure an 8,9-methylenedioxy group can exhibit topoisomerase I-targeting activity. Structure-activity studies were performed to examine the influence of saturation at the 11,12-positions of several substituted 8,9-methylenedioxybenzo[i]phenanthridines. The activities of these dihydro analogues were compared to those of their unsaturated analogues. In addition, the influence of varying substituents at the 2- and 3-positions within the A-ring of these 8,9-methylenedioxybenzo[i]phenanthridines on their relative potency as topoisomerase I-targeting agents and cell proliferation as determined using the MTT assay was investigated. 2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine and its 11,12-dihydro derivative were among the more potent analogues evaluated with regard to topoisomerase I-targeting activity and cytotoxicity.
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U2 - 10.1016/S0968-0896(03)00394-8
DO - 10.1016/S0968-0896(03)00394-8
M3 - Article
C2 - 12901925
AN - SCOPUS:0041620599
VL - 11
SP - 3795
EP - 3805
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 17
ER -