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.
- 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: [email protected].
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.