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

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 (<b>4a</b>–<b>g</b>, <b>5a</b>–<b>h</b>, <b>6a</b>–<b>h</b>, and <b>7a</b>–<b>h</b>) and bioevaluated their <i>in vitro</i> activity against human cancer cell lines (NCI-H23, ACHN, MDA-MB-231, PC-3, NUGC-3, and HCT 15). Among all synthesized scaffolds, <b>6g</b> 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