Chinese Journal of Organic Chemistry >
Synthesis and Antitumor Activity of Novel 3,3'-((4-Chloro-2H-thiochromen-3-yl)methylene)bis(1H-indole)-Like Topoisomerase II Inhibitors
Received date: 2023-11-23
Revised date: 2024-01-18
Online published: 2024-03-05
Supported by
2023 Medical Science of Hebei Province(20231748)
A series of 3,3'-((4-chloro-2H-thiochromen-3-yl)methylene)bis(1H-indole) analogues containing bisindole and benzothiopyran structures were designed and synthesized by docking and splicing groups with known bioactive structures. Antitumor assay against six tumor cell lines of the target compounds were screened and the results indicate that 3,3'-(4-chloro- 2H-thioene-3-yl)methylene)bis(5-methoxy-1H-indole) (5b), 3,3'-(4-chloro-7-methyl-2H-thioene-3-yl)methylene)bis(5-methyl- 1H-indole) (5f), and 3,3'-(4-chloro-7-methyl-2H-thioene-3-yl)methylene)bis(N-methyl-2-methylindole) (5g) showed good anti- proliferative activity against tumor cells. The results of topoisomerase inhibition assay showed that compounds 5b, 3,3'-(4-chloro-2H-thioene-3-yl)methylene)bis(6-cyano-1H-indole) (5c), 5f and 5g showed selective inhibitory activity against DNA topoisomerase II, while other compounds showed different levels of DNA topoisomerase II inhibition activity. The results of molecular docking studies indicated that compounds 5b and 5g had stable binding with DNA topoisomerase II, which had potential research value for antitumor drugs.
Key words： bisindole; antitumor; DNA topoisomerase II; molecular docking
Guochao Liang , Tingting Dong , Haiying Ji , Chunyan Wang , Yali Song , Wei Zhang . Synthesis and Antitumor Activity of Novel 3,3'-((4-Chloro-2H-thiochromen-3-yl)methylene)bis(1H-indole)-Like Topoisomerase II Inhibitors[J]. Chinese Journal of Organic Chemistry, 2024 , 44(6) : 1949 -1956 . DOI: 10.6023/cjoc202311023
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