Synthesis, cytotoxic activities and structure-activity relationships of topoisomerase I inhibitors: indolizinoquinoline-5,12-dione derivatives.
A series of indolizinoquinoline-5,12-dione derivatives (IQDs) are synthesized and evaluated for their cytotoxic activities toward human lung adenocarcinoma (GLC-82), large-cell lung carcinoma (NCI-H460), promyelocytic leukemia (HL-60) and breast carcinoma (MCF-7) cells by MTT method. Most of the IQDs show significant cytotoxic potency. In addition, the evaluation of structure-activity relationships indicated that the incorporation of electron-withdrawing substituents at the C or D ring will enhance the activities of the target compounds distinctly. The topoisomerase I inhibitory activity is also measured.
Cheng
Yu
Y
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
An
Lin-Kun
LK
Wu
Ning
N
Wang
Xiao-Dong
XD
Bu
Xian-Zhang
XZ
Huang
Zhi-Shu
ZS
Gu
Lian-Quan
LQ
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D004791:Enzyme Inhibitors; D007211:Indoles; D011804:Quinolines; D059004:Topoisomerase I Inhibitors; C037219:quinoline; D004264:DNA Topoisomerases, Type I