Exploring Novel Coumarin-Tethered Bis-Triazoles: Apoptosis Induction in Human Pancreatic Cancer Cells, Antimicrobial Effects, and Molecular Modelling Investigations

In the present study, we identified that two representative compounds (7 c and 9 f) of our newly synthesized coumarin-tagged bis-triazoles induced apoptosis in human pancreatic cells (PANC-1) by caspase 3/7mediated pathway. Both 7 c and 9 f (IC₅₀=7.15±1.19 and 6.09±0.79 μM, respectively) were found to be ~100 times superior against PANC-1 as compared to the standard drug Gemcitabine (IC₅₀=>500 μM), without showing any toxicity to the normal pancreatic epithelial cells (H6C7). Molecular docking studies further endorsed them as potential pancreatic cancer therapeutics due to their strong hydrogen bonding interactions with the epidermal growth factor receptor (EGFR) enzyme, which is overexpressed in cancerous cells including pancreatic cancer. Additionally, these compounds also showed moderate inhibitory activity against a panel of microbial strains. Overall, our findings reveal that the coumarin hybrids 7 c and 9 f are viable chemotypes to be adopted as templates for the development of new anticancer drugs, particularly against pancreatic cancer.