ANTICANCER EFFICACY OF MAGAININ2 AND ANALOG PEPTIDES

Linear helical channel-forming peptides structurally similar to the Xe nopus-derived antibiotic, Magainin2-amide, were synthesized. Because a ctivity resides in the physicochemical properties of the peptides, an all-D-amino acid as well as an all-L-amino acid sequence were tested f or anticancer activity. In vitro activity against carcinoma cells and in vivo efficacy against four murine ascites tumors were determined. T he novel peptides proved to have enhanced potency in vitro and in vivo as compared to the parent compound. The 50% inhibitory concentrations against A549 cells for the all-D, the all-L, and Magainin2 were 6, 10 , and 110 mug/ml, respectively. All three peptides had activity agains t P388 leukemia, S180 ascites, and a spontaneous ovarian tumor when in jected i.p. Increase in life span of over 100% was produced for the an alogues in the latter two models. The maximally effective concentratio ns for the analogues were 20 to 25 mg/kg while Magainin2 required 50-6 0 mg/kg for in vivo efficacy. The all-D-amino acid peptide, MSI-238, p roved as effective as doxorubicin at a more advanced stage of the ovar ian tumor and this activity may be attributed to its resistance to pro teolytic degradation. Therefore, this class of amphiphilic alpha-helic al cationic peptides has potential in the peritoneal treatment of ovar ian cancer.