3-(6-Phenylimidazo [2,1- b][1,3,4]thiadiazol-2-yl)-1 H-Indole Derivatives as New Anticancer Agents in the Treatment of Pancreatic Ductal Adenocarcinoma

Molecules. 2020 Jan 14;25(2):329. doi: 10.3390/molecules25020329.

Abstract

A new series of imidazo[2,1-b][1,3,4]thiadiazole derivatives was efficiently synthesized and screened for their in vitro antiproliferative activity on a panel of pancreatic ductal adenocarcinoma (PDAC) cells, including SUIT-2, Capan-1 and Panc-1. Compounds 9c and 9l, showed relevant in vitro antiproliferative activity on all three pre-clinical models with half maximal inhibitory concentration (IC50) ranging from 5.11 to 10.8 µM, while the compounds 9e and 9n were active in at least one cell line. In addition, compound 9c significantly inhibited the migration rate of SUIT-2 and Capan-1 cells in the scratch wound-healing assay. In conclusion, our results will support further studies to increase the library of imidazo [2,1-b][1,3,4] thiadiazole derivatives for deeper understanding of the relationship between biological activity of the compounds and their structures in the development of new antitumor compounds against pancreatic diseases.

Keywords: antiproliferative activity; imidazo[2,1-b][1,3,4]thiadiazole derivatives; indole compounds; migration assay; pancreatic cancer; resistance.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Proliferation*
  • Drug Screening Assays, Antitumor
  • Humans
  • Indoles / chemistry*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Indoles

Supplementary concepts

  • Pancreatic Carcinoma