Scholarlink

<p>A series of novel 3-chloro-1H-indazole-based 1,3,4-thiadiazole derivatives (<b>1–15</b>) were synthesized, characterized and evaluated for their inhibitory activity against thymidine phosphorylase and α-glucosidase. Several compounds showed potent dual inhibition, with compound <b>4</b> exhibiting the highest activity (IC<sub>50</sub> = 4.70 ± 1.34&#xa0;µM for thymidine phosphorylase and IC<sub>50</sub> = 1.38 ± 0.46&#xa0;µM for α-glucosidase), surpassing the standard inhibitors 7-deazaxanthine (IC<sub>50</sub> = 12.42 ± 1.27&#xa0;µM) and acarbose (IC<sub>50</sub> = 5.97 ± 0.35&#xa0;µM). Moreover, other synthesized derivatives included compounds 9, 2, 1 and 6 all showing improved inhibition profiles. Structure activity relationship analysis revealed that the nature and position of substituents on the phenyl ring play a critical role in modulating the enzyme inhibition potential. Similarly, molecular docking confirmed favorable binding interactions with the active sites of both enzymes, while ADMET profiling indicated good drug-likeness and pharmacokinetic potential. These findings suggest that thiadiazole-indazole hybrids represent promising lead candidates for the development of dual targets enzymes inhibitors with potential therapeutic applications in metabolic and proliferative disorders.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Facile 3-chloro-1H-indazole based 1,3,4-thiadiazole derivatives as novel thymidine phosphorylase and anti-diabetic inhibitors: Experimental, in-vitro and molecular modelling approaches

  • 期刊论文

  • 发表日期：

    2025年7月19日

查看全文
  • Yousaf Khan,
  • Aneela Maalik,
  • Wajid Rehman,
  • Hina Sarfraz,
  • Rafaqat Hussain,
  • Shoaib Khan,
  • Marouan Kouki,
  • Aisha Usman,
  • Rubina Adnan

摘要

A series of novel 3-chloro-1H-indazole-based 1,3,4-thiadiazole derivatives (1–15) were synthesized, characterized and evaluated for their inhibitory activity against thymidine phosphorylase and α-glucosidase. Several compounds showed potent dual inhibition, with compound 4 exhibiting the highest activity (IC50 = 4.70 ± 1.34 µM for thymidine phosphorylase and IC50 = 1.38 ± 0.46 µM for α-glucosidase), surpassing the standard inhibitors 7-deazaxanthine (IC50 = 12.42 ± 1.27 µM) and acarbose (IC50 = 5.97 ± 0.35 µM). Moreover, other synthesized derivatives included compounds 9, 2, 1 and 6 all showing improved inhibition profiles. Structure activity relationship analysis revealed that the nature and position of substituents on the phenyl ring play a critical role in modulating the enzyme inhibition potential. Similarly, molecular docking confirmed favorable binding interactions with the active sites of both enzymes, while ADMET profiling indicated good drug-likeness and pharmacokinetic potential. These findings suggest that thiadiazole-indazole hybrids represent promising lead candidates for the development of dual targets enzymes inhibitors with potential therapeutic applications in metabolic and proliferative disorders.