5-nitro-thiophene-thiosemicarbazone derivative induces cell death, cell cycle arrest, and phospho-kinase shutdown in pancreatic ductal adenocarcinoma cells

Abstract

IntroductionPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options. This study explores the potential of novel 5-nitro-thiophene-thiosemicarbazone derivatives as therapeutic agents for PDAC. MethodsWe evaluated the cytotoxicity of seven derivatives in peripheral blood mononuclear cells (PBMCs) and PDAC cell lines. Promising candidates (PR12 and PR17) were further analyzed for their effects on colony formation, cell cycle progression, and reactive oxygen species (ROS) production. PR17, the most promising derivative, was subjected to additional investigation, including analysis of autophagy-related genes and protein kinase inhibition. ResultsThree derivatives (PR16, PR19, and PR20) displayed cytotoxicity towards PBMCs. PR12 reduced colony formation and G0/G1 cell cycle arrest in PDAC cells. Notably, PR17 exhibited potent activity in MIA PaCa-2 cells, inducing S-phase cell cycle arrest, downregulating autophagy genes, and inhibiting key protein kinases. ConclusionPR17, a 5-nitro-thiophene-thiosemicarbazone derivative, demonstrates promising antineoplastic activity against PDAC cells by potentially modulating cell cycle progression, autophagy, and protein kinase signaling. Further studies are warranted to elucidate the detailed mechanism of action and explore its efficacy in vivo.