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

Created on 17 Jul 2026

Authors

Basant G Salib, Basma M Essa, Hesham A Shamsel-Din, Mohamed A Motaleb, M El-Tawoosy, Adli A Selim, Sameh Ahmed Rizk, Ahmed Hassan Ibrahim Faraag, Mohamed A Ali, Islam Yousif Mostafa, Reda Mansour, Salah S Elyan, Mohamed Salah Basiouny, Kurls E Anwer

Published in

Molecular diversity. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

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.

PMID:
42467310
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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