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

ID: ALA4823319

Journal: Bioorg Med Chem

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

Authors: Sim S, Lee S, Ko S, Phuong Bui B, Linh Nguyen P, Cho J, Lee K, Kang JS, Jung JK, Lee H.

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.

CiteXplore: 34500188

DOI: 10.1016/j.bmc.2021.116371

Patent ID: ┄