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

  • ACS Med Chem Lett. 2016 Feb 16;7(4):385-90. doi: 10.1021/acsmedchemlett.6b00004.
Hyeju Jo  1 ,  Minho Choi  1 ,  Arepalli Sateesh Kumar  1 ,  Yeongeun Jung  1 ,  Sangeun Kim  1 ,  Jieun Yun  2 ,  Jong-Soon Kang  2 ,  Youngsoo Kim  1 ,  Sang-Bae Han  1 ,  Jae-Kyung Jung  1 ,  Jungsook Cho  3 ,  Kiho Lee  4 ,  Jae-Hwan Kwak  5 ,  Heesoon Lee  1
Affiliations
  • 1. Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  • 2. Korea Research Institute of Bioscience and Biotechnology , Ochang 363-883, Republic of Korea.
  • 3. College of Pharmacy, Dongguk University , Goyang 410-773, Republic of Korea.
  • 4. College of Pharmacy, Korea University , Sejong 339-700, Republic of Korea.
  • 5. College of Pharmacy, Kyungsung University , Busan 608-736, Republic of Korea.
PMID: 27096046 DOI: 10.1021/acsmedchemlett.6b00004
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.

Keywords
1,2,3,4-Tetrahydroquinolines; NF-κB inactivation; human cancer cell lines; in vitro cytotoxicity.