Pancreatic cancer is the fourth leading cause of cancer death in the United States. The prognosis of the disease is very negative, because the cancer will be usually metastasized by the time a patient manifests symptoms. Although combination therapy shows some promise, new drugs to treat the disease are needed. Given our interest in finding new therapies for pancreatic cancer, we sought to determine whether the known cytotoxic activity of the batzellines extended to pancreatic cancer cell lines. The batzellines are pyrroloiminoquinones alkaloids obtained from the deep-water Caribbean sponge Batzella sp (family Esperiopsidae, order Poecilosclerida). We show here that batzellines exhibit selective cytotoxicity towards the pancreatic cancer cell lines AsPC-1, Panc-1, BxPC-3, and MIA PaCa2 compared with the normal African green monkey kidney epithelial cell line Vero. The batzellines cause cytotoxicity by inducing cell cycle arrest that is mediated by their ability to intercalate into DNA and/or inhibit topoisomerase II activity. The cytotoxic abilities of isobatzellines A and C against pancreatic cancer cell lines, their low toxicity against normal cells, and their reported ability to be synthesized makes them interesting compounds with potential chemotherapeutic effects that may merit further research.