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Design, synthesis, and biological activity of TLR7-based compounds for chemotherapy-induced alopecia

  • Jincheng YangEmail author
  • Kun Chen
  • Bin Wang
  • Liudi Wang
  • Shuya Qi
  • Weihua Wang
PRECLINICAL STUDIES
  • 57 Downloads

Summary

Hair loss is a common dermatosis symptom and side-effect in cancer chemotherapeutics. Imiquimod application at mid and late telogen activated the hair follicle stem cells leading to premature hair cycle entry. Based on quinoline structure, a newly synthesized compound 6b displayed proliferation activity in vitro and in vivo through branch chain replacement and triazole ring cyclization. Toll-like receptors (TLRs) are also critical mediators of the immune system, and their activation is linked to various diseases. The present study aimed to expand new agonists within co-crystallization of TLR7 (PDB code: 5GMH); however, biological assays of NF-κB activity and NO-inhibition indicated that five selected compounds were TLR7 antagonists. Molecular docking indicated the binding mode differences: antagonists binding TLR7 in a different direction and interacting with adjacent TLR7 with difficulty in forming dimers.

Keywords

TLR7 Hair follicle stem cell Chemotherapy-induced alopecia Antagonist Synthesis 

Notes

Acknowledgements

The key structures have applied Chinese patent. (CN201711279295, CN108003153A).

We thank Zhejiang Ruyao Biotech Co.,LTD for technologic support.

Funding

The work was supported by National Natural Science Foundation of China (No. 81603218).

Compliance with ethical standards

Conflict of interest

Author Jincheng Yang declares that he has no conflict of interest. Author Kun Chen declares that she has no conflict of interest. Author Bin Wang declares that he has no conflict of interest. Author Liudi Wang declares that she has no conflict of interest. Author Shuya Qi declares that she has no conflict of interest. Author Weihua Wang declares that she has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. Animal experiments were approved by the Institutional Animal Care and Use Committee at National Cancer Center, Chinese Academy of Medical Sciences. (NCC2016A050, 9 March 2016) All applicable international, national, and institutional guidelines for the care and use of animals were followed.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.State Key Laboratory of Molecular Oncology/Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  3. 3.Clinical Stem Cell CenterThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina

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