biostudies-literaturePecoraro CItalian Ministry of University and Research (MUR)327https://www.ebi.ac.uk/biostudies/studies/S-EPMC12387776biostudies-literatureUnknown23(8)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 micrMarine drugsNew Marine-Inspired Oxadiazole Derivatives for Use Against Pancreatic Ductal Adenocarcinoma.PMC12387776202243KSPJ_001Pecoraro CCarbone DDiana PLencioni GParrino BVahabi MGiovannetti EAl Ostoot FHMfalseNew Marine-Inspired Oxadiazole Derivatives for Use Against Pancreatic Ductal Adenocarcinoma.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 micr2025-01-01T00:00:00Z2025 Aug2026-04-08T10:34:45.113Z2026-04-08T01:29:34.659ZS-EPMC123877764086364410.3390/md23080327