Design, Synthesis and Biological Evaluation of Novel Catalpol Derivatives as Potential Pancreatic Cancer Inhibitors

A series of C10-position imidazole-modified catalpol derivatives are specifically designed and synthesized for serving as potential pancreatic cancer inhibitors, which are characterized by 1 H NMR, 13 C NMR and high-resolution mass spectrometry (HRMS). They were evaluated by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) test on two human pancreatic cancer cells PANC-1, BxPC-3 and normal pancreatic cell HPDE6-C7, which showed the significant inhibitory effected on the growth of human pancreatic cancer cells of PANC-1 and BxPC-3, especially 91.6% efficacy on BxPC-3, and 73.1% on PANC-1. Simulation studies like molecular docking supported strong binding of vascular endothelial growth factor receptor 2 (VEGFR-2) protein tyrosine kinase (PDB ID: 4AGD), a target of pancreatic cancer. A novel imidazol-modified catalpol compound 3i with strong inhibitory effect on pancreatic cancer cells, which could potentially develop into anti-pancreatic cancer drug candidates in the future.