Antibacterial Activity of Amino Acid-Modified Cationic Dendrimers Loaded with a Mixture of Two Triterpenoid Acids

Searching for new devices capable to counteract the growing bacterial resistance, we reported the remarkable antimicrobial activity against several Gram-negative species of cationic dendrimers (CD), modified with lysine and histidine, also establishing that their cationic character, due to the lysine content, is essential for their potency. To develop new antibacterial agents, possibly active against Gram-positive species, cationic dendrimer complexes containing arginine and lysine, and trapping ursolic and oleanolic acids (UOACDs), two natural triterpenoids known for their activity against Gram-positive bacteria, were considered here as excellent candidates. Three selected UOACDs were tested unsuccessfully against Gram-negative strains, but successfully against 12 Gram-positive clinical isolates. The preliminary results obtained, in terms of MIC values, established that the antibacterial activity observed for UOACDs strongly depended on the number of cationic groups and the type of peripheral amino acids present in the CDs, and was attributable only to CDs and not to the presence and release of UOA. Lysine was critical for potency, while arginine redirected activity against Gram-positive species. A high cationic character, associated with the balanced content of lysine/arginine, produced a remarkable antimicrobial effect (MIC = 0.5–8.7 µM). More indepth investigations are underway to better characterize the activity of the developed arginine-containing CDs.