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ACS medicinal chemistry letters
Apr 14, 2016;7 (4): 385-90.

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

Hyeju Jo, Minho Choi, Arepalli Sateesh Kumar, Yeongeun Jung, Sangeun Kim, Jieun Yun, Jong-Soon Kang, Youngsoo Kim, Sang-Bae Han, Jae-Kyung Jung, Jungsook Cho, Kiho Lee, Jae-Hwan Kwak, Heesoon Lee
Author Information
  1. Hyeju Jo: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  2. Minho Choi: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  3. Arepalli Sateesh Kumar: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  4. Yeongeun Jung: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  5. Sangeun Kim: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  6. Jieun Yun: Korea Research Institute of Bioscience and Biotechnology , Ochang 363-883, Republic of Korea.
  7. Jong-Soon Kang: Korea Research Institute of Bioscience and Biotechnology , Ochang 363-883, Republic of Korea.
  8. Youngsoo Kim: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  9. Sang-Bae Han: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  10. Jae-Kyung Jung: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
  11. Jungsook Cho: College of Pharmacy, Dongguk University , Goyang 410-773, Republic of Korea.
  12. Kiho Lee: College of Pharmacy, Korea University , Sejong 339-700, Republic of Korea.
  13. Jae-Hwan Kwak: College of Pharmacy, Kyungsung University , Busan 608-736, Republic of Korea.
  14. Heesoon Lee: Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, 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

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