Design, synthesis, and biological evaluation of potent 1,2,3,4-tetrahydroisoquinoline derivatives as anticancer agents targeting NF-κB signaling pathway

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Title
Design, synthesis, and biological evaluation of potent 1,2,3,4-tetrahydroisoquinoline derivatives as anticancer agents targeting NF-κB signaling pathway
Author(s)
S Sim; S Lee; S Ko; B PP Bui; P L Nguyen; J Cho; K Lee; Jong Soon Kang; J K Jung; H Lee
Bibliographic Citation
Bioorganic & Medicinal Chemistry, vol. 46, pp. 116371-116371
Publication Year
2021
Abstract
The multifunctional transcription factor, nuclear factor-κB (NF-κB), is broadly involved in multiple human diseases, such as cancer and chronic inflammation, through abnormal modulations of the NF-κB signaling cascades. In patients with several types of cancer diseases, NF-κB is excessively activated, which could result in the stimulation of proliferation and/or suppression of apoptosis. Herein, we present a new series of 1,2,3,4-tetrahydroisoquinoline derivatives with good anticancer activities against various human cancer cell lines, which are rationally designed based on our novel NF-κB inhibitors. The SAR studies demonstrated that compound 5d with a methoxy group at the R3 position exhibits the most anti-proliferative activity with GI50 values, ranging 1.591 to 2.281 μM. Similar to KL-1156, the compound 5d (HSR1304) blocked NF-κB nuclear translocation step in LPS-stimulated MDA-MB-231 cells, probably leading to cytotoxic potency against tumor cells. Together with known potent NF-κB inhibitors containing diverse core heterocyclic moieties, the 1,2,3,4-tetrahydroisoquinoline derivatives can provide structural diversity, enhancing a potential for the development of a novel class of anticancer drugs.
Keyword
NF-κB signalingAnticancer activity1,2,3,4-TetrahydroisoquinolineHuman cancer cell linesNF-κB nuclear translocation
ISSN
0968-0896
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bmc.2021.116371
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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