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Introduction <p>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.</p> Materials and methods <p>In this study, 10 scaffolds based on Glu-Ureido-linked thiazolidinone-based ligands were designed and 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 NMA-based dynamics.</p> Results <p>The selected molecules are screened based on target prediction, DFT, toxicity and other selected parameters. Among the screened compounds, PSMA-THL02, PSMA-THL06, PSMA-THL07, PSMA-THL08, and PSMA-THL09 exhibited the lowest binding energy scores and passed other parameters, indicating them as potent scaffolds for the PSMA.</p> Discussion <p>The good docking score, ADMET and other physicochemical properties suggest that Glu-Ureido-linked thiazolidinone scaffolds are promising candidates for PSMA-targeted imaging. Among the libraries, the PSMA-THL02, PSMA-THL06, PSMA-THL07, PSMA-THL08, and PSMA-THL09 are the computationally 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 selected candidates as potent scaffolds for imaging and therapeutics.</p> Conclusion <p>Among the selected libraries, the Glu-Ureido-based thiazolidinone ligands, particularly PSMA-THL02, PSMA-THL06, PSMA-THL07, PSMA-THL08 and PSMA-THL09, are computationally 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.</p>

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In-silico study of thiazolidinone-linked Glu-Ureido based PSMA ligands for PET application

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月15日

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  • Mohd. Faheem,
  • Vaibhav Pandey,
  • Manisha Prasad,
  • Manish Dixit

摘要

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, 10 scaffolds based on Glu-Ureido-linked thiazolidinone-based ligands were designed and 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 NMA-based dynamics.

Results

The selected molecules are screened based on target prediction, DFT, toxicity and other selected parameters. Among the screened compounds, PSMA-THL02, PSMA-THL06, PSMA-THL07, PSMA-THL08, and PSMA-THL09 exhibited the lowest binding energy scores and passed other parameters, indicating them as potent scaffolds for the PSMA.

Discussion

The good docking score, ADMET and other physicochemical properties suggest that Glu-Ureido-linked thiazolidinone scaffolds are promising candidates for PSMA-targeted imaging. Among the libraries, the PSMA-THL02, PSMA-THL06, PSMA-THL07, PSMA-THL08, and PSMA-THL09 are the computationally 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 selected candidates as potent scaffolds for imaging and therapeutics.

Conclusion

Among the selected libraries, the Glu-Ureido-based thiazolidinone ligands, particularly PSMA-THL02, PSMA-THL06, PSMA-THL07, PSMA-THL08 and PSMA-THL09, are computationally 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.