Scholarlink

Purpose <p>Leishmaniasis, a neglected tropical disease, has minimal treatment options, that is also complicated by drug toxicity and resistance. This study aimed to design and evaluate new thiazole-based benzenesulfonamide derivatives to improve antileishmanial activity and overcome current therapeutic limitations.</p> Methods <p>A series of 4-substituted-N-(4-substitutedphenylthiazol-2-yl)benzenesulfonamides was designed using a 2-sulfonamide scaffold. Molecular docking and ADMET predictions helped choose which compounds to synthesize and for the following in vitro antileishmanial screening.</p> Results <p>Among the synthesized compounds, 4&#xa0;F, 4I, and 4&#xa0;A showed strong potency with IC₅₀ values of 0.009 µM, 0.01 µM, and 0.08 µM, respectively. These values were much lower than that of the standard drug Miltefosine (IC₅₀ = 8.2 µM). Structure–activity relationship analysis highlighted the important contribution of electron-donating groups at the R₁ position and bulky hydrophobic substituents at R₂ in improving bioactivity.</p> Conclusion <p>The present study introduces thiazole–benzenesulfonamide as a novel hybrid against Leishmania, a scaffold not previously explored for this indication. Compared to reported antileishmanial agents, the designed derivatives (compound 4&#xa0;F, 4I, and 4&#xa0;A) demonstrated superior potency and selectivity compared to Miltefosine, while molecular docking provided mechanistic insights into their interactions with key parasite targets. These findings highlight the novelty and therapeutic significance of this scaffold for the advancement of antileishmanial drug discovery.</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

Design and Development of Substituted Thiazole-2-Benzenesulfonamides as Novel Antileishmanial Agents

  • 期刊论文

  • 发表日期：

    2026年1月29日

查看全文
  • Arjun Modi,
  • Roshani Patel,
  • Hitesh J. Vekariya

摘要

Purpose

Leishmaniasis, a neglected tropical disease, has minimal treatment options, that is also complicated by drug toxicity and resistance. This study aimed to design and evaluate new thiazole-based benzenesulfonamide derivatives to improve antileishmanial activity and overcome current therapeutic limitations.

Methods

A series of 4-substituted-N-(4-substitutedphenylthiazol-2-yl)benzenesulfonamides was designed using a 2-sulfonamide scaffold. Molecular docking and ADMET predictions helped choose which compounds to synthesize and for the following in vitro antileishmanial screening.

Results

Among the synthesized compounds, 4 F, 4I, and 4 A showed strong potency with IC₅₀ values of 0.009 µM, 0.01 µM, and 0.08 µM, respectively. These values were much lower than that of the standard drug Miltefosine (IC₅₀ = 8.2 µM). Structure–activity relationship analysis highlighted the important contribution of electron-donating groups at the R₁ position and bulky hydrophobic substituents at R₂ in improving bioactivity.

Conclusion

The present study introduces thiazole–benzenesulfonamide as a novel hybrid against Leishmania, a scaffold not previously explored for this indication. Compared to reported antileishmanial agents, the designed derivatives (compound 4 F, 4I, and 4 A) demonstrated superior potency and selectivity compared to Miltefosine, while molecular docking provided mechanistic insights into their interactions with key parasite targets. These findings highlight the novelty and therapeutic significance of this scaffold for the advancement of antileishmanial drug discovery.