2. Academic Validation
  3. Design, synthesis and biological evaluation of new parbendazole derivatives for the treatment of HNSCC

Design, synthesis and biological evaluation of new parbendazole derivatives for the treatment of HNSCC

  • Eur J Med Chem. 2022 Aug 5:238:114450. doi: 10.1016/j.ejmech.2022.114450.
Dong Liang 1,  Chen Yu 1,  Zhao Ma 1,  Mingzhao Hu 1,  Jiahui Wang 1,  Xuhui Dong 1,  Lupei Du 1,  Minyong Li 2
Affiliations

Affiliations

  • 1 Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 2 Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address: mli@sdu.edu.cn.
PMID: 35576703 DOI: 10.1016/j.ejmech.2022.114450
Abstract

Head and neck squamous cell carcinoma (HNSCC) is a lethal disease with a terrible prognosis, accounting for more than 900,000 new cases and 500,000 deaths each year, nevertheless, its pharmacotherapy is rather limited. Parbendazole was previously identified as a potential HNSCC therapy candidate in our research. Herein, we report the discovery of two series of parbendazole derivatives as tubulin inhibitors. Structure-activity relationship (SAR) analyses led to the discovery of compound 9q with the best pharmacological activities and pharmacokinetic properties. This compound exhibited reasonable inhibition activity on cell proliferation (HN6, CAL-27, Fadu) and tubulin polymerization, induced cell Apoptosis, blocked cell cycle and suppressed cell migration and invasion. Compound 9q also displayed low toxicity and a favorable therapeutic effect on a xenograft tumor, indicating that it is a promising starting point for further research.

Keywords

HNSCC; Parbendazole; Tubulin polymerization inhibitors.

Figures