Ecofriendly Synthesis of New Azo Compounds as Antibacterial Agents: In Vitro Screening and Preliminary In Vivo...

This work is designed to establish sustainable routes for the synthesis of new variable azo heterocyclic derivatives via the reaction of 2-[(dicyanomethyl)diazinyl]benzoic acid 2 with different nucleophilic agents, including hydrazine derivatives (such as phenyl hydrazine and 2,4-dinitrophenylhydrazine), acylhydrazines (e.g., benzoylhydrazine), nitrogen-based nucleophiles (semicarbazide and thiosemicarbazide), oxygen-containing reagents (hydroxylamine), as well as urea, thiourea, guanidine hydrochloride, and o-phenylenediamine. Both conventional heating and microwave approaches were used to furnish the desired heterocycles. The compounds exhibited potent antibacterial activity against Gram-positive and Gram-negative pathogens, outperforming fluconazole. The lead compound was successfully radiolabeled with ¹³¹I in high yield (87.72% RCY). In vivo evaluation in an infection model demonstrated excellent pharmacokinetics, with specific uptake in infected tissue (13.7% ID/g at 1 h) and a high target-to-non-target ratio (6.31). These findings underscore the theranostic potential of these azo compounds, positioning them as both antimicrobial agents and candidate radiotherapeutics for infection.