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<p>A novel series of 2-(4-aminoquinolyl) and 1-aminoadamantyl-substituted 4,6-dimethoxy-1,3,5-triazine derivatives has been designed, synthesized, and evaluated for anti-HIV activity. Molecular docking studies indicated that the most active derivatives interact at the allosteric site of HIV-1 reverse transcriptase, forming key interactions with critical residues, including TYR181, TYR188, TYR381, LYS101, LYS103, VAL106, PHE227, and PRO236, essential for enzymatic inhibition. Among the synthesized compounds, <b>8a</b> emerged as the most potent molecule, demonstrating an IC<sub>50</sub> of 1.92 ± 0.35&#xa0;nM and a selectivity index (SI) of 52.08, outperforming the standard drug Nevirapine, which exhibited an IC<sub>50</sub> of 1.99 ± 0.26&#xa0;nM and an SI of 50.25. Furthermore, ADMET screening confirmed that <b>8a</b> exhibits minimal organ toxicity and no signs of cytotoxicity, highlighting its safety profile for potential therapeutic use. Computational analysis using Density Functional Theory (DFT) further revealed that the incorporation of chloroquinoline and 1-aminoadamantyl moieties plays a crucial role in enhancing the anti-HIV activity of the compound. These findings suggest that <b>8a</b> represents a promising scaffold for future anti-HIV-1 drug development, offering an effective combination of potency, selectivity, and safety.</p>

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Design, Synthesis and Anti-HIV Evaluation of Novel 1,3,5-triazine based Aminoquinolyl and Aminoadmantyl Derivatives

  • 期刊论文

  • 发表日期：

    2026年2月11日

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  • Jyoti Kumawat,
  • Sonika Jain,
  • Pankaj Kumar Jain,
  • Saraswati Patel,
  • Gulshan Kumar,
  • Jaya Dwivedi,
  • Dharma Kishore

摘要

A novel series of 2-(4-aminoquinolyl) and 1-aminoadamantyl-substituted 4,6-dimethoxy-1,3,5-triazine derivatives has been designed, synthesized, and evaluated for anti-HIV activity. Molecular docking studies indicated that the most active derivatives interact at the allosteric site of HIV-1 reverse transcriptase, forming key interactions with critical residues, including TYR181, TYR188, TYR381, LYS101, LYS103, VAL106, PHE227, and PRO236, essential for enzymatic inhibition. Among the synthesized compounds, 8a emerged as the most potent molecule, demonstrating an IC50 of 1.92 ± 0.35 nM and a selectivity index (SI) of 52.08, outperforming the standard drug Nevirapine, which exhibited an IC50 of 1.99 ± 0.26 nM and an SI of 50.25. Furthermore, ADMET screening confirmed that 8a exhibits minimal organ toxicity and no signs of cytotoxicity, highlighting its safety profile for potential therapeutic use. Computational analysis using Density Functional Theory (DFT) further revealed that the incorporation of chloroquinoline and 1-aminoadamantyl moieties plays a crucial role in enhancing the anti-HIV activity of the compound. These findings suggest that 8a represents a promising scaffold for future anti-HIV-1 drug development, offering an effective combination of potency, selectivity, and safety.