Adli AbdAllah Selim

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.

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 ¹³¹ I 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.

This study aimed to develop sustainable synthetic routes for novel enaminonitrile pyridine derivatives and evaluate a lead compound's potential as a dual-action theranostic agent for oncology, combining targeted therapy and diagnostic imaging. Two green chemistry techniques were utilized: microwave-assisted and solvent-free mechanochemical grinding. The lead compound 7, was assessed for in vitro anticancer activity against MCF-7 cells. It was radiolabeled with iodine-131, optimizing parameters like substrate amount and pH. Finally, in vivo biodistribution and tumor targeting were studied in tumor-bearing mice. The green synthesis was highly efficient. Compound 7 showed superior anticancer activity (IC50 = 3.77 ± 0.43 µM) versus cisplatin. Radiolabeling achieved high radiochemical purity (95.74 ± 1.44%). Biodistribution studies confirmed excellent, selective tumor uptake (9.07% ID/g at 1 h) with sustained retention (7.91% ID/g at 24 h) and high target-to-background ratios. This work successfully establishes efficient green synthesis routes. Compound 7 is a potent and selective sustainable theranostic agent, effectively merging green chemistry principles with precision oncology applications for both therapy and diagnosis.

Alpha therapy (TAT) relies on combining alpha-emitting radionuclides with specific cell-targeting vectors to deliver a high payload of cytotoxic radiation capable of destroying tumor tissues. TAT efficacy comes from the tissue selectivity of the targeting vector, the high linear energy transfer (LET) of the radionuclide, and the short range of alpha particles in tissues. Recent research studies have been directed to evaluate TAT on a preclinical and clinical scale, including evaluating damage to tumor tissues with minimal toxic radiation effects on surrounding healthy tissues. This review highlights the use of Actinium-225/Bismuth-213 radionuclides as promising candidates for TAT. Herein, we begin with a discussion on the production and supply of [²²⁵Ac]Ac/[²¹³Bi]Bi followed by the formulation of [²²⁵Ac]Ac/[²¹³Bi]Bi-radiopharmaceuticals using different radiolabeling techniques. Finally, we have summarized the preclinical and clinical evaluation of these potential radiotheranostic agents.

Biocompatible silver nanoparticles (AgNPs) are employed with an active ingredient of milk thistle extract, silybin (SIB), to treat cancers. Strong cytotoxic effects of SIB‐AgNPs against two distinct cell lines (MCF‐7 and HepG2) are observed on a stable nano‐platform that contains spherical nanoparticles within a limited size range. With a high radiochemical purity, radioiodination of SIB‐AgNPs was accomplished. The investigation on the biodistribution of [¹³¹I]iodo‐SIB‐AgNPs in mice‐bearing tumors showed that SIB‐AgNPs prefer localization in tumor tissue. In conclusion, this work strengthens the case for [¹³¹I]iodo‐SIB‐AgNPs as an effective theranostic agent for tumor imaging and treatment.

Sulfonamide derivatives are a significant class of medicinal compounds. Gold nanoparticles (AuNPs) offer precise cancer treatment through targeted delivery, boasting high drug-loading capacity and low toxicity. This study aimed to develop and evaluate 99mTc-labeled benzenesulfonamide derivative-entrapped gold citrate nanoparticles as a tumor-targeting agent. A novel benzenesulfonamide derivative bearing a pyridine moiety was synthesized. Compound 3 (4-((3-cyano-4-(2,4-dichlorophenyl)-6-phenylpyridin-2-yl)amino)-N-(diaminomethylene)benzenesulfonamide) exhibited remarkable anti-cancer activity against MCF-7 cells. The chemical reduction method was employed to create compound 3-citrate-AuNPs. A comprehensive examination of the synthesized nano-platform was conducted, including zeta potential, size analysis, radiochemical yield, and in-vivo biodistribution in tumor-bearing mice. The nano-platform was successfully produced with good stability, optimal particle size (9 nm diameter for AuNPs), and high radiochemical purity for [^99mTc]Tc-compound 3 (88.31 ± 2.14%). In-vivo investigations revealed that intravenously administered [99mTc]Tc-compound 3-citrate-AuNPs accumulated in tumors with a high target-to-non-target ratio. The findings validate the efficacy of the novel [^99mTc]Tc-compound 3-citrate-AuNPs platform as a tumor-targeting agent.