Polyalkylguanidines: new weapons to tackle bacterial resistance

In this historical period known as the antibiotic crisis era, the ever faster rise of bacterial strains resistant to the clinically used antibiotics along with the scientific research silent gap in the antibacterial field is treating seriously to the worldwide public health. Hence, we urgently need to develop new antibacterials agents with an innovative mode of action, able to trick the mechanisms of the pathogen resistance. In this alarming frame, aware of the antibacterial properties of guanidine moieties, Prof. M. Botta and his research group have evaluated the biological activity of a linear polyalkylguanidino series, synthesized for different medicinal purpose, toward a panel of bacterial microorganisms. Only one compound (1) emerged to have an interesting broad-spectrum antibacterial activity. Later, the serendipitous discovery that the test batch of compound 1 was actually a mixture of oligomers led us to identify the chemical structure of the main component, dimer 2, which was the responsible for the activity. From its scaffold, we designed and synthesized a small library of analogs to make some preliminary consideration on the pharmacophores with the aim of improving the selectivity index and studying the mode(s) of action.