New Marine-Inspired Oxadiazole Derivatives for Use Against Pancreatic Ductal Adenocarcinoma.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with limited effective therapeutic options due to late diagnosis, aggressive progression, and rapid development of drug resistance. In pursuit of novel treatments, this study reports the design, synthesis, and biological evaluation of a new series of topsentin derivatives, featuring a 1,2,4-oxadiazole core. The newly synthesized derivatives were screened for antiproliferative activity against multiple PDAC cell lines (SUIT-2, Patu-T, and PANC-1), identifying several compounds with potent growth-inhibitory effects, particularly on SUIT-2 and Patu-T cells. Further studies demonstrated that these compounds also significantly inhibited cell migration and reduced clonogenic potential, with IC₅₀ values in the micromolar range. The results suggest that these marine-inspired 1,2,4-oxadiazole derivatives effectively target key hallmarks of PDAC, including proliferation, migration, and colony formation, supporting their further development as promising candidates for overcoming drug resistance and metastatic progression in pancreatic cancer.