Antimicrobial activity and DNA/BSA binding study of new silver(I) complexes with 1,8-naphthyridine

Silver(I) compounds are well known for their pharmacological applications as antibiotics and have been also evaluated as potential anticancer agents. The use of simple silver(I) salts, such as AgNO₃, as an antimicrobial agent, has been limited due to the formation of AgCl precipitate under the physiological conditions, preventing a major part of Ag(I) ions to reach the infected site. On the other hand, a slow and maintainable release of Ag(I) ion into the infected cell or tissue could be achieved by its administration in the form of complexes. Among different classes of ligands used for the synthesis of biologically active silver(I) complexes, a special attention was devoted to the aromatic nitrogen-containing heterocycles. Considering this, in the present study, we have synthesized two new silver(I) complexes with 1,8-naphthyridine (1,8-naph), polynuclear [Ag(CF₃SO₃)(1,8-naph)]_n (Ag1) and dinuclear [Ag(1,8-naph)(H₂O)]₂(PF₆)₂ (Ag2), and evaluated their antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as Candida spp. The obtained results revealed that these silver(I) complexes showed significant activity toward the Gram-positive Staphylococcus aureus and Candida spp. The values of binding constants of Ag1 and Ag2 to BSA are high enough to indicate their interaction to this biomolecule, but not so strong to prevent their release upon arrival to the target site. The partition coefficient (logP) values for Ag1 and Ag2 are -0.14 and 0.37, respectively, what is in accordance with those for pharmacophores in the Comprehensive Medicinal Chemistry database. Тhe investigated silver(I) complexes inside the cell could interact with DNA through the non-intercalative (electrostatic) mode.