Polynuclear Silver(I)-Quinoxaline Complex: Comprehensive Structural Characterization, Antimycobacterial Properties...

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Biophysics

Background:

• Silver(I) complexes with aromatic heterocyclic ligands exhibit significant antimicrobial properties.
• These properties are linked to their ability to interact with biological targets.
• Aromatic heterocyclic ligands are crucial components in developing novel antimicrobial agents.

Purpose of the Study:

• Synthesize and characterize a new polynuclear silver(I) complex with N-(3"-phenylpropyl)quinoxaline-2-carboxamide (pqx-2ca).
• Evaluate the antimycobacterial activity of the synthesized complex.
• Investigate the molecular mechanisms underlying the complex's activity, including DNA and protein interactions.

Main Methods:

• Single-crystal X-ray diffraction for structural confirmation.
• Spectroscopic techniques (NMR, IR, UV-Vis) for characterization.
• Density Functional Theory (DFT) calculations and spectral simulations for solution behavior analysis.
• Antimycobacterial activity assays against various Mycobacterium species.
• Molecular docking studies to assess binding to DNA, bovine serum albumin (BSA), and mycobacterial targets (InhA, MmpL3).

Main Results:

• Successfully synthesized and structurally characterized the polynuclear silver(I) complex [Ag(NO3)(pqx-2ca)]n.
• The complex exhibited significantly enhanced antimycobacterial activity against Mycobacterium tuberculosis H37Ra, M. smegmatis, M. aurum, M. avium, and M. kansasii compared to the free ligand.
• Experimental and docking studies confirmed stable binding to the minor groove of DNA and subdomain III of BSA.
• Docking revealed inhibitory potential against InhA and MmpL3 proteins, with binding affinities comparable to standard inhibitors.

Conclusions:

• The synthesized silver(I) complex [Ag(NO3)(pqx-2ca)]n demonstrates potent antimycobacterial efficacy.
• The complex possesses a dual mechanism of action, targeting both DNA and essential mycobacterial proteins.
• [Ag(NO3)(pqx-2ca)]n is a promising candidate for developing novel silver-based antimycobacterial agents.