Antitumor and antimicrobial activity of some cyclic tetrapeptides and tripeptides derived from marine bacteria

Abstract

Marine derived cyclo(Gly-L-Ser-L-Pro-L-Glu) was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-L-His-L-Pro-L-Glu). Cyclic tetrapeptides (CtetPs) were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays. The benzyl group protected CtetPs derivatives, showed better activity against antibiotic-resistant Staphylococcus aureus in the range of 60-120 μM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity against several cell lines at a concentration of 80-108 μM. However, shortening the size of the ring to the cyclic tripeptide (CtriP) scaffold, cyclo(Gly-L-Ser-L-Pro), cyclo(Ser-L-Pro-L-Glu) and their analogues showed no antibiotic or antitumor activity. This phenomenon can be explained from their backbone structures.