Synthesis, 131I-radioiodination, and biodistribution of a novel nicotinonitrile derivative with in vitro antimicrobial and DNA gyrase inhibitory activities.

To address the rise of multidrug-resistant bacteria by developing novel antibacterial agents with integrated capabilities for targeted delivery and real-time tracking, and to evaluate their potential for infection theranostics. Novel enaminonitrile-based pyridine and pyran derivatives were sustainably synthesized. Among them, lead compound 5 was assessed for in vitro DNA gyrase inhibition. Compound 5 was then radiolabeled with iodine-131, and radiolabeling yield was measured. In vivo biodistribution and pharmacokinetic profile were evaluated using an inflammatory murine model, with target-to-muscle ratios calculated. Compound 5 showed potent DNA gyrase inhibition (IC50 = 11.31 µg/mL). Radiolabeling produced [131I]I-5 with high radiolabeling yield (90.15%). In the murine model, the radiolabeled construct demonstrated rapid blood clearance and sustained, specific accumulation at the infection site, achieving a high target-to-muscle ratio of 5.18 at 1-h post-administration. This study introduces a new class of antibacterial agents and successfully translates a lead compound into a theranostic formulation. [131I]I-5 shows strong promise as a candidate for image-guided therapy and targeted treatment of infectious diseases.