Toll-like receptor 2 antagonists identified through virtual screening and experimental validation

Prasannavenkatesh Durai, Hyeon Jun Shin, Asma Achek, Hyuk Kwon Kwon, Rajiv Gandhi Govindaraj, Suresh Panneerselvam, Dhanusha Yesudhas, Jiwon Choi, Kyoung Tai No, Sangdun Choi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Toll-like receptor 2 (TLR2) antagonists are key therapeutic targets because they inhibit several inflammatory diseases caused by surplus TLR2 activation. In this study, we identified two novel nonpeptide TLR2 antagonists, C11 and C13, through pharmacophore-based virtual screening. At 10 μm, the level of interleukin (IL)-8 inhibition by C13 and C11 in human embryonic kidney TLR2 overexpressing cells was comparable to the commercially available TLR2 inhibitor CU-CPT22. In addition, C11 and C13 acted in mouse macrophage-like RAW 264.7 cells as TLR2-specific inhibitors and did not suppress the tumor necrosis factor-α induction by TLR3 and TLR4 activators. Moreover, the two identified compounds bound directly to the human recombinant TLR2 ectodomain, during surface plasmon resonance analysis, and did not affect cell viability in a 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay. In total, two virtually screened molecules, C11 and C13, were experimentally proven to be effective as TLR2 antagonists, and thus will provide new insights into the structure of TLR2 antagonists, and pave the way for the development of TLR2-targeted drug molecules.

Original languageEnglish
Pages (from-to)2264-2283
Number of pages20
JournalFEBS Journal
Volume284
Issue number14
DOIs
Publication statusPublished - 2017 Jul 1

Fingerprint

Toll-Like Receptor 2
Screening
Surface Plasmon Resonance
Molecules
Macrophages
Interleukin-8
Surface plasmon resonance
Cell Survival
Tumor Necrosis Factor-alpha
Assays
Chemical activation
Cells
Kidney

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Durai, P., Shin, H. J., Achek, A., Kwon, H. K., Govindaraj, R. G., Panneerselvam, S., ... Choi, S. (2017). Toll-like receptor 2 antagonists identified through virtual screening and experimental validation. FEBS Journal, 284(14), 2264-2283. https://doi.org/10.1111/febs.14124
Durai, Prasannavenkatesh ; Shin, Hyeon Jun ; Achek, Asma ; Kwon, Hyuk Kwon ; Govindaraj, Rajiv Gandhi ; Panneerselvam, Suresh ; Yesudhas, Dhanusha ; Choi, Jiwon ; No, Kyoung Tai ; Choi, Sangdun. / Toll-like receptor 2 antagonists identified through virtual screening and experimental validation. In: FEBS Journal. 2017 ; Vol. 284, No. 14. pp. 2264-2283.
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Durai, P, Shin, HJ, Achek, A, Kwon, HK, Govindaraj, RG, Panneerselvam, S, Yesudhas, D, Choi, J, No, KT & Choi, S 2017, 'Toll-like receptor 2 antagonists identified through virtual screening and experimental validation', FEBS Journal, vol. 284, no. 14, pp. 2264-2283. https://doi.org/10.1111/febs.14124

Toll-like receptor 2 antagonists identified through virtual screening and experimental validation. / Durai, Prasannavenkatesh; Shin, Hyeon Jun; Achek, Asma; Kwon, Hyuk Kwon; Govindaraj, Rajiv Gandhi; Panneerselvam, Suresh; Yesudhas, Dhanusha; Choi, Jiwon; No, Kyoung Tai; Choi, Sangdun.

In: FEBS Journal, Vol. 284, No. 14, 01.07.2017, p. 2264-2283.

Research output: Contribution to journalArticle

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AU - Durai, Prasannavenkatesh

AU - Shin, Hyeon Jun

AU - Achek, Asma

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AU - Govindaraj, Rajiv Gandhi

AU - Panneerselvam, Suresh

AU - Yesudhas, Dhanusha

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AU - No, Kyoung Tai

AU - Choi, Sangdun

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Durai P, Shin HJ, Achek A, Kwon HK, Govindaraj RG, Panneerselvam S et al. Toll-like receptor 2 antagonists identified through virtual screening and experimental validation. FEBS Journal. 2017 Jul 1;284(14):2264-2283. https://doi.org/10.1111/febs.14124