Scholarlink

<p>Leishmaniasis remains a significant global health challenge, driven by limited therapeutic options and rising drug resistance, underscoring the need for novel, selective anti-leishmanial agents. Trypanothione reductase (TR), a key enzyme involved in the redox homeostasis of Leishmania parasites, represents an attractive and selective molecular target for anti-leishmanial drug discovery. In the present study, a series of N2-substituted 1,2,3-triazole derivatives (TZ1–TZ40) was rationally designed using a target-based drug design strategy. All compounds were subjected to molecular docking against <i>Leishmania</i> TR to evaluate binding affinity and key enzyme–ligand interactions, followed by in silico ADME prediction to assess drug-likeness and pharmacokinetic suitability. Based on favourable docking scores and acceptable ADME profiles, seven compounds (TZ1–TZ7) were selected for chemical synthesis. The synthesized compounds were screened for anti-leishmanial potential against promastigote and amastigote forms. Among them, compound TZ1 exhibited the most promising activity, with IC₅₀ values of 2.9 ± 0.3 µM against amastigotes and 3.9 ± 0.4 µM against promastigotes, supported by stable docking interactions and suitable ADME characteristics. However, its potential as a novel anti-leishmanial lead compound needs to be further investigated through trypanothione reductase enzymatic assay and in vivo antileishmanial assay.</p> Graphical abstract <p></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

N2-substituted triazoles as trypanothione reductase inhibitors: in silico evaluation, synthesis, and anti-leishmanial activity

  • 期刊论文

  • 发表日期：

    2026年7月8日

查看全文
  • Mahender Thatikayala,
  • Sanjeev Kumar Sahu

摘要

Leishmaniasis remains a significant global health challenge, driven by limited therapeutic options and rising drug resistance, underscoring the need for novel, selective anti-leishmanial agents. Trypanothione reductase (TR), a key enzyme involved in the redox homeostasis of Leishmania parasites, represents an attractive and selective molecular target for anti-leishmanial drug discovery. In the present study, a series of N2-substituted 1,2,3-triazole derivatives (TZ1–TZ40) was rationally designed using a target-based drug design strategy. All compounds were subjected to molecular docking against Leishmania TR to evaluate binding affinity and key enzyme–ligand interactions, followed by in silico ADME prediction to assess drug-likeness and pharmacokinetic suitability. Based on favourable docking scores and acceptable ADME profiles, seven compounds (TZ1–TZ7) were selected for chemical synthesis. The synthesized compounds were screened for anti-leishmanial potential against promastigote and amastigote forms. Among them, compound TZ1 exhibited the most promising activity, with IC₅₀ values of 2.9 ± 0.3 µM against amastigotes and 3.9 ± 0.4 µM against promastigotes, supported by stable docking interactions and suitable ADME characteristics. However, its potential as a novel anti-leishmanial lead compound needs to be further investigated through trypanothione reductase enzymatic assay and in vivo antileishmanial assay.

Graphical abstract