Identification of Human Toll-like Receptor 2-Agonistic Activity in Dihydropyridine-Quinolone Carboxamides

Ziwei Hu, Janardhan Banothu, Mallesh Beesu, Collin J. Gustafson, Michael J.H. Brush, Kathryn L. Trautman, Alex C.D. Salyer, Balaji Pathakumari, Sunil A. David

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-N-(pyridin-3-ylmethyl)-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure-activity relationship studies on the carboxamide moiety led to the identification of analogues that induce chemokines and cytokines in a TLR2-dependent manner. These results represent new leads for the development of vaccine adjuvants.

Original languageEnglish (US)
Pages (from-to)132-136
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume10
Issue number1
DOIs
StatePublished - Oct 1 2019

Bibliographical note

Funding Information:
*Phone: (612) 625-3848. E-mail: sdavid@umn.edu. ORCID Sunil A. David: 0000-0003-1655-4641 Author Contributions ‡These authors contributed equally. Funding This work was supported by NIH/NIAID contract HHSN272201400056C. Notes The authors declare no competing financial interest.

Publisher Copyright:
© 2018 American Chemical Society.

Keywords

  • Toll-like receptor 2
  • Vaccine adjuvants
  • chemokines
  • cytokines
  • dihydropyridine-quinolones

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