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 (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.
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Hyeju
H
Jo
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Minho
M
Choi
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Arepalli Sateesh
AS
Kumar
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Yeongeun
Y
Jung
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Sangeun
S
Kim
Korea Research Institute of Bioscience and Biotechnology , Ochang 363-883, Republic of Korea.
Jieun
J
Yun
Korea Research Institute of Bioscience and Biotechnology , Ochang 363-883, Republic of Korea.
Jong-Soon
JS
Kang
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Youngsoo
Y
Kim
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Sang-Bae
SB
Han
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Jae-Kyung
JK
Jung
College of Pharmacy, Dongguk University , Goyang 410-773, Republic of Korea.
Jungsook
J
Cho
College of Pharmacy, Korea University , Sejong 339-700, Republic of Korea.
Kiho
K
Lee
College of Pharmacy, Kyungsung University , Busan 608-736, Republic of Korea.
Jae-Hwan
JH
Kwak
Department of Pharmacy, Chungbuk National University , Chungbuk 362-763, Republic of Korea.
Heesoon
H
Lee
1,2,3,4-Tetrahydroquinolines; NF-κB inactivation; human cancer cell lines; in vitro cytotoxicity