The Prostate cancer (PC) is a major problem all over worldwide and this is the second highest cancer-related mortality rate after lung cancer all over worldwide. At least 299,010 likely cases in men were reported in the US in 2024 and about 35,250 deaths are reported. The overexpression of prostate-specific membrane antigen (PSMA) is a key factor in the progression of prostate cancer and contributes to metastasis in lymph nodes, soft tissues and bones metastasis. The numerous studies have reported that, Glu-ureido-based molecules exhibit high binding affinity for PSMA. The earliest imaging agents developed from this structure were labeled with radioactive halogen isotopes and demonstrated nanomolar binding affinity, leading to exceptional imaging properties. Hence the Glu-ureido chemical moiety is a very important template as inhibitor of PSMA. In this study to explore the chemical structural and electronic features of Glu-Ureido structure with the aid of quantum chemistry computer simulations. In this study, first optimized the structure of this chemical structure using the B3LYP 6311-G (++, d, p) basis set. In this study investigated the maximal quantity of electronic charge transfer (N_max), chemical hardness (η), electrostatic potential, chemical potential (µ) and electrophilicity (ω). By the using Natural Bond Orbital (NBO) analysis, the examination shows that the molecule’s chemically active regions π-electron-electron delocalization within the molecule that contribute to its stability.

The FDA approved rufinamide, chemically 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide, a triazole-based scaffold, as an anticonvulsant drug in 2008. It is mainly used to treat seizures associated with Lennox–Gastaut Syndrome (LGS). The exact mechanism of rufinamide is unknown, but some literature reported that rufinamide works by regulating the brain’s sodium channel activity, which aids in maintaining the stability of neuronal membranes and averting the overabundance of electrical activity. In the view of computational chemistry, the amide group, fluorine atom, and triazole ring are the specific parts of this skeleton and play an important role in action with the receptor. This study explored computerized simulations of quantum chemistry techniques to investigate the chemical structure and electrical properties of rufinamide. An optimizing structure started the quantum calculation through the B3LYP 6311-G (++, d, p) basis set, explored along with investigating the maximal quantity of electronic charge transfer (N_max), chemical hardness (η), electrostatic potential, chemical potential (µ), and electrophilicity (ω). The Natural Bond Orbital (NBO) analysis-based observation reveals that the molecule’s chemically active regions have hyperconjugated electron interactions within the molecule, which contributes to the molecule’s stability. This study explores the role of the amide group and difluoro-substituted phenyl group in chemical structure and in binding property with the receptor of the Ca²⁺–and voltage-activated K⁺ channel.

Epilepsy is a multifactorial neurological disorder characterized by recurrent, unprovoked seizures. Although various diagnostic approaches are available, no single technique serves as a gold standard. Radiotracer-based positron emission tomography (PET) offers a non-invasive strategy for localizing epileptic foci. However, the currently available tracers have limited specificity and pharmacokinetic performance. In this work, report the radiosynthesis and preliminary evaluation of [¹⁸F]rufinamide as a potential PET tracer for epilepsy imaging. Microwave-assisted (µE) radiosynthesis (120 °C, 20 min) afforded quantitative conversion with a total synthesis time of 40 min from the end of bombardment (EOB), and a two-step procedure completed with 20 ± 5%, radiochemical yield and >95% radiochemical purity. The physicochemical profiling revealed a lipophilic nature (log D_7.4) and high plasma protein binding (82.5 ± 2.1%). PET imaging and biodistribution studies in normal Wistar rats confirmed brain uptake and renal clearance. These findings demonstrate that [¹⁸F]rufinamide possesses favorable radiochemical and pharmacological characteristics, supporting its potential as a novel PET probe for non-invasive imaging of epileptic brain regions.

Introduction: The Prostate Specific Membrane Antigen (PSMA) is a type II transmembrane glycoprotein known as Glutamate Carboxypeptidase II, overexpressed in prostate carcinoma. The Glu-Ureido moiety is a target-specific inhibitor for PSMA, and these widely used inhibitors show promising results in both non-invasive nuclear imaging and radionuclide-based therapeutic applications for prostate cancer. Materials and Methods In this study, 60 scaffolds based on Glu-Ureido-linked thiazolidinone-based ligands were designed and 10 ligands were virtually screened using various in-silico parameters. These designed scaffolds incorporated fluorine atoms to mimic radiolabelling approaches and evaluate their potential as imaging agents. The compounds were evaluated using DFT, ADMET profiling, toxicity analysis, molecular docking and dynamics. Results The selected molecules are screened based on target prediction, DFT, toxicity and other selected parameters. Among the screened compounds, PSMA-THL02, PSMA-THL04, PSMA-THL06, PSMA-THL07, PSMA-THL08 and PSMA-THL10 exhibited the lowest binding energy scores and passed other parameters, indicating them as potent scaffolds for the PSMA. Discussion The good docking score and other physicochemical properties suggest that Glu-Ureido-linked thiazolidinone scaffolds are promising candidates for PSMA-targeted imaging. Among the library, the PSMA-THL02, PSMA-THL06, PSMA-THL07, PSMA-THL08, and PSMA-THL10 are the promising scaffolds for prostate cancer imaging. The presence of fluorine atoms not only simulates potential radionuclide tagging but may also enhance receptor binding and molecular stability. These findings support the potent scaffolds for imaging and therapeutics from the selected candidates. Conclusion Among the selected library, the Glu-Ureido-based thiazolidinone ligands, particularly PSMA-THL02, THL04, THL06, THL07, THL08, and THL10, are potent scaffolds with specificity toward PSMA. These scaffolds represent promising candidates for future development as diagnostic and therapeutic radiotracers in the management of prostate cancer.