期刊
BIOORGANIC CHEMISTRY
卷 114, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2021.105114
关键词
1,4-Dihydropyrazolo[4,3-b]indoles; C-N bond formation; Cadogan Cyclization; DFT study; Cancer; Topoisomerase inhibitors
资金
- DST-Inspire, New Delhi [IF 180460]
- SERB, Delhi [EMR/2017/002702]
A new synthetic route for 1,4-dihydropyrazolo[4,3-b]indoles was reported, and the resulting compounds showed cytotoxicity against various cancer cell lines, potentially acting as selective inhibitors of Topo I or Topo II.
We herein report a new synthetic route for a series of unreported 1,4-dihydropyrazolo[4,3-b]indoles (6-8) via deoxygenation of o-nitrophenyl-substituted N-aryl pyrazoles and subsequent intramolecular (sp(2))-N bond formation under microwave irradiation expedite modified Cadogan condition. This method allows access to NH-free as well as N-substituted fused indoles. DFT study and controlled experiments highlighted the role of nitrene insertion as one of the plausible reaction mechanisms. Furthermore, the target compounds exhibited cytotoxicity at low micromolar concentration against lung (A549), colon (HCT-116), and breast (MDA-MB-231, and MCF-7) cancer cell lines, induced the ROS generation and altered the mitochondrial membrane potential of highly aggressive MDA-MB-231 cells. Further investigations revealed that these compounds were selective Topo I (6h) or Topo II (7a, 7b) inhibitors.
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