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

Abstract 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.