Nucleobase Ionic Liquids (NBILs) Induced Apoptosis via Caspase 3 Activation andin silico Regulation of the IRE1a Pathway in Pancreatic Cancer PANC-1 Cells

Introduction: Globally rising incidences of pancreatic cancer, a leading cause of death, have made it imperative to explore new chemotherapeutic agents, such as ionic liquids (ILs), as an emerging class of anticancer agents. Nucleobase ionic liquids (NBILs) have shown great promise against pancreatic cancer PANC-1 cells. This study aims to synthesize purine and pyrimidine nucleobase ionic liquids (NBILs) and evaluate their in vitro anticancer activity on PANC-1 cells to gain valuable insights into the anticancer potential of NBILs. Methods: Comprehensive in vitro studies, including flow cytometric apoptosis analysis, reverse transcription polymerase chain reaction (RT-PCR), gene expression studies, and molecular docking analysis, were performed to demonstrate the potent anticancer effects of NBILs. Results: A series of nucleobase ionic liquids (NBILs) was synthesized using a multi-step protocol. Significant anti-pancreatic cancer activity was observed for the synthesized NBILs against PANC-1 cells, with compound 14b showing high expression of CASP3 and a high percentage of apoptosis. Discussion: Molecular mechanism and in silico studies demonstrated remarkable anti-pancreatic cancer activity of NBILs via activation of CASP3 and regulation of the IRE1a pathway. The research highlights the future potential for utilizing NBILs against pancreatic cancer PANC-1 cells. Conclusion: NBILs displayed significant anti-pancreatic cancer activity through apoptosis induction via activation of Caspase 3 and in silico regulation of the IRE1a pathway in pancreatic cancer PANC-1 cells.