Polynuclear silver(I)–quinoxaline complex : comprehensive structural characterization, antimycobacterial properties and DNA/BSA binding study

Bouz, Ghada (author), Stevanović, Nevena Lj. (author), Počkaj, Marta (author), Andrejević, Tina P. (author), Turel, Iztok (author), Jand’ourek, Ondřej (author), Konečná, Klára (author), Milanović, Žiko (author), Milisavljević, Kristina (author), Glišić, Biljana (author)

Background: Silver(I) complexes with aromatic heterocyclic ligands are well known for their broad antimicrobial potential, largely attributed to their ability to interact with biomolecular targets. Results and Discussion: In this study, a new polynuclear silver(I) complex with N-(3′-phenylpropyl)quinoxaline-2-carboxamide (pqx-2ca), [Ag(NO$_3$)(pqx-2ca)]$_n$, was synthesized. Its structure was confirmed by single-crystal X-ray diffraction and comprehensively characterized using NMR, IR, and UV–Vis spectroscopy, while its behavior in solution was further elucidated through density functional theory (DFT) calculations combined with spectral simulations. The complex demonstrated significantly enhanced antimycobacterial activity compared with the free ligand when tested against the avirulent Mycobacterium tuberculosis H37Ra, fast-growing model organisms M. smegmatis and M. aurum, as well as the nontuberculous species M. avium and M. kansasii. Experimental and docking studies confirmed stable binding of the complex to subdomain III of bovine serum albumin (BSA) and to the minor groove of DNA. Furthermore, docking to validated mycobacterial targets revealed inhibitory potential toward the InhA and MmpL3 proteins, with binding affinities comparable to those of standard inhibitors. Conclusions: These results highlight [Ag(NO$_3$)(pqx-2ca)]$_n$ as a promising candidate for the development of silver-based antimycobacterial agents with a dual mechanism of action involving both DNA and protein targets.

• Language: English
• Keywords: N-substituted quinoxaline-2-carboxamides, silver(I) complexes, antimycobacterial activity, DNA interaction, protein interaction
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 26 str.
• Numbering: Vol. 18, iss. 2, art. 169
• PID: 20.500.12556/RUL-179689
• UDC: 546.571:547.83
• ISSN on article: 1999-4923
• DOI: 10.3390/pharmaceutics18020169
• COBISS.SI-ID: 266427651
• Publication date in RUL: 20.02.2026

Record is a part of a journal

• Title: Pharmaceutics
• Shortened title: Pharmaceutics
• Publisher: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: N-substituirani kinoksalin-2-karboksamidi, srebrovi(I) kompleksi, antimikrobna aktivnost, interakcije z DNA, interakcija s proteini