Multimodal synthetic approaches to a pyrazole-based derivative: preliminary antibacterial screening, 131I-radiolabeling, and biodistribution in an inflammation model.

Abstract

A series of 1-methyl-4-(aryldiazenyl)-1H-pyrazole-3,5-diamine derivatives (2-12) was designed and synthesized using microwave-assisted, grinding, and conventional heating techniques. The structures of the synthesized compounds were confirmed by infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. The antibacterial activity of the synthesized derivatives was evaluated against Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8739), and Klebsiella pneumoniae (ATCC 13883) using the agar well diffusion method. Compound 2 showed activity against all four tested strains, with inhibition zones of 25 ± 0.9 mm against B. subtilis, 16 ± 0.5 mm against S. aureus, 19 ± 0.6 mm against E. coli, and 16 ± 0.9 mm against K. pneumoniae. Compound 2 was selected for radiolabeling with 131I as a representative neutral, lipophilic derivative, on the basis of its activity profile, favorable lipophilicity, and structural suitability for electrophilic radioiodination. The radioiodinated compound 2 was obtained with a radiolabeling yield of 88.12 ± 2.6% and exhibited high radiochemical stability in saline (88.12% at 24 h, 86.11% at 48 h) and moderate stability in serum (85.93% at 24 h, 81.14% at 48 h). Following intravenous administration, in vivo biodistribution studies in inflammation-bearing mice demonstrated rapid blood clearance, higher uptake at the inflamed site than in the contralateral healthy tissue, and sustained retention, with a maximum uptake of 12.77 ± 0.69% ID/g at 60 min post-injection and a maximum target-to-nontarget (T/NT) ratio of 5.85 at 30 min. These findings provide a basis for further evaluation of [131I]I-compound 2 as a potential inflammation probe.

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