Structure-activity relationship study of a series of novel oxazolidinone derivatives as IL-6 signaling blockers

  • Bioorg Med Chem Lett. 2016 Feb 15;26(4):1282-6. doi: 10.1016/j.bmcl.2016.01.016.
Sarbjit Singh  1 ,  Veeraswamy Gajulapati  2 ,  Kondaji Gajulapati  2 ,  Ja-Il Goo  2 ,  Yeon-Hwa Park  3 ,  Hwa Young Jung  2 ,  Sung Yoon Lee  2 ,  Jung Ho Choi  4 ,  Young Kook Kim  4 ,  Kyeong Lee  5 ,  Tae-Hwe Heo  3 ,  Yongseok Choi  6
Affiliations
  • 1. College of Phamacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea; College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
  • 2. College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
  • 3. College of Phamacy, The Gatholic University of Korea, Bucheon 420-743, Republic of Korea.
  • 4. Natural Medicine Reasearch Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea.
  • 5. College of Phamacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea.
  • 6. College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea. Electronic address: [email protected].
PMID: 26810262 DOI: 10.1016/j.bmcl.2016.01.016
Abstract

A series of Oxazolidinone and indole derivatives were synthesized and evaluated as IL-6 signaling blockers by measuring the effects of these compounds on IL-6-induced luciferase expression in human hepatocarcinoma HepG2 cells transfected with p-STAT3-Luc. Among different compounds screened, compound 4d was emerged as the most potent IL-6 signaling blockers with IC50 value of 5.9 μM which was much better than (+)-Madindoline A (IC50=21 μM), a known inhibitor of IL-6.

Keywords
IL-6 antagonists; IL-6 signaling inhibitor; Oxazolidinone; Rheumatoid arthritis; STAT3; gp130.