Development of Novel 1,2,3,4-Tetrahydroquinoline Scaffolds as Potent NF-κB Inhibitors and Cytotoxic Agents

Abstract

1,2,3,4-Tetrahydroquinolines have been identified as the most potent inhibitors of LPS-induced NF-κB transcriptional activity. To discover new molecules of this class with excellent activities, we designed and synthesized a series of novel derivatives of 1,2,3,4-tetrahydroquinolines (4a−g, 5a−h, 6a−h, and 7a−h) and bioevaluated their in vitro activity against human cancer cell lines (NCI-H23, ACHN, MDA-MB-231, PC-3, NUGC-3, and HCT 15). Among all synthesized scaffolds, 6g exhibited the most potent inhibition (53 times that of a reference compound) of LPS-induced NF-κB transcriptional activity and the most potent cytotoxicity against all evaluated human cancer cell lines.

Progress in the Chemistry of Tetrahydroquinolines

“…1-Acyl-2-benzamido-1,2,3,4-tetrahydroquinolines 56 were identified as potent inhibitors of the lipopolysaccharide (LPS)-induced transcriptional activity of the NF-κB factor, which is involved in many processes, including the regulation of cellular growth and apoptosis (Figure ). Some of these compounds showed sub-micromolar activity against a variety of human cancer cell lines …”

Suppression of Pax3–MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide

“…THQC was synthesized with more than 99% purity as previously described [ 43 ]. Pharmacological agents were arbutin (Sigma-Aldrich, St. Louis, MO, USA) as a skin whitener, ensulizole (Sigma-Aldrich) as a UVB absorber, and H-89 (Sigma-Aldrich) as a PKA inhibitor.…”

Design, synthesis, and antitumor evaluation of novel methylene moiety-tetheredtetrahydroquinoline derivatives

“…In recent years, tetrahydroquinolines (THQs) have been considered to be one of the pharmaceutical agents that have the greatest interest in the chemistry of quinolines due to their broad biological and pharmacological activities [4][5][6][7]. The most potent effects among a variety of pharmacological activities are exhibited by 1,2,3,4-THQs [8][9][10][11][12], such as glucocorticoid receptor agonists [13], antagonists of vasopressin V 2 receptor [14], and antitumor agents targeting the colchicine site on tubulin [15]. A second type of THQ with the 5,6,7,8-THQ structure has appeared in some reports in which their potential biopharmaceutical effects were evaluated [16][17][18].…”