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<p>Earlier therapeutic strategies primarily focused on combating diseases caused by external pathogens; recent advancements have highlighted the pivotal role of endogenous enzymes in the progression of non-infectious disorders. Enzymes such as urease&#xa0; and thymidine phosphorylase&#xa0; &#xa0;have been implicated in various pathological conditions, prompting the need for effective enzyme-targeted inhibitors. In this study, a novel series of bis-thiazole linked linked Schiff Bases&#xa0; <b>(1–10)</b> was designed and synthesized as potential dual enzyme inhibitors. The structural integrity of the synthesized compounds was confirmed by FTIR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR and HRMS&#xa0; analyses. The derivatives were screened for their inhibitory activity against urease and thymidine phosphorylase. Among them, the synthesized analogues 4, 5, 7, and 8 exhibited significant activity, surpassing the reference inhibitors thiourea&#xa0; (IC<sub>50</sub> = 13.45 ± 0.95 µM) and 7-deazaxanthine&#xa0; (IC<sub>50</sub> = 17.61 ± 0.92 µM). In particular, compound-8&#xa0; emerged as the most potent dual inhibitor, with IC<sub>50</sub> values of 8.20  ± 0.98  M and 9.29 ± 0.51 µM against urease and thymidine phosphorylase, respectively. To elucidate the binding mechanism, molecular docking studies were conducted, revealing favorable interactions between the active compounds and key residues within the active sites of the target enzymes. These findings suggest that the bis-thiazole linked Schiff Bases scaffold holds strong potential as a promising chemotype for the development of future enzyme-inhibiting therapeutics.</p>

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Design, synthesis and biological profiling of bis-thiazole linked Schiff bases as effective enzyme inhibitors for targeting urease and thymidine phosphorylase proteins

  • 期刊论文

  • 发表日期：

    2026年1月15日

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  • Yousaf Khan,
  • Hina Sarfraz,
  • Mahrukh Naseem,
  • Rubina Adnan,
  • Syeda Farwa Naqvi,
  • Azmatullah Khan,
  • Urooba Gulshan,
  • Syed Aminullah

摘要

Earlier therapeutic strategies primarily focused on combating diseases caused by external pathogens; recent advancements have highlighted the pivotal role of endogenous enzymes in the progression of non-infectious disorders. Enzymes such as urease  and thymidine phosphorylase   have been implicated in various pathological conditions, prompting the need for effective enzyme-targeted inhibitors. In this study, a novel series of bis-thiazole linked linked Schiff Bases  (1–10) was designed and synthesized as potential dual enzyme inhibitors. The structural integrity of the synthesized compounds was confirmed by FTIR, 1H-NMR, 13C-NMR and HRMS  analyses. The derivatives were screened for their inhibitory activity against urease and thymidine phosphorylase. Among them, the synthesized analogues 4, 5, 7, and 8 exhibited significant activity, surpassing the reference inhibitors thiourea  (IC50 = 13.45 ± 0.95 µM) and 7-deazaxanthine  (IC50 = 17.61 ± 0.92 µM). In particular, compound-8  emerged as the most potent dual inhibitor, with IC50 values of 8.20  ± 0.98  M and 9.29 ± 0.51 µM against urease and thymidine phosphorylase, respectively. To elucidate the binding mechanism, molecular docking studies were conducted, revealing favorable interactions between the active compounds and key residues within the active sites of the target enzymes. These findings suggest that the bis-thiazole linked Schiff Bases scaffold holds strong potential as a promising chemotype for the development of future enzyme-inhibiting therapeutics.