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Abstract <p><b>Objective:</b> Dihydropyrimidinone–isatin derivatives exhibit a wide range of biological activities, including antifungal, antibacterial, antitumor, and anticancer properties. Due to the deregistration of all existing antinemic compounds, our research group aims to identify new compounds with potent nematicidal activity. <b>Methods:</b> A one-pot nucleophilic addition of urea and a 1,3-dicarbonyl compound to the C-3 position of isatin was performed to obtain spiro(DHPM-isatin) derivatives. These were characterized using <sup>1</sup>H, <sup>13</sup>C NMR, FT-IR spectroscopy, and mass spectrometry. The synthesized derivatives were evaluated for their ovicidal and larvicidal potential against the plant pathogen <i>Meloidogyne incognita</i>. <b>Results and Discussion:</b> The spiro(DHPM-isatin) derivative (<b>IVe</b>) exhibited significant inhibition of egg hatching, achieving 98.00% inhibition at 1500 ppm after 168 h, along with notable larvicidal activity. In contrast, derivative (<b>IVf</b>) showed exceptional efficacy, causing 100% juvenile mortality at 168 h at concentrations of 750 ppm and above, along with pronounced inhibition of egg hatching. Furthermore, <i>in silico</i> studies conducted on five <i>M. incognita</i> proteins—carboxylic ester hydrolase, cytochrome c oxidase, putative aspartate protease, ATP synthase, and cytochrome <i>b</i>—revealed that the tested derivatives (<b>IVa–IVh</b>) effectively bind to the amino acid residues Tyr, Glu, Arg, His, Ala, Asp, Ser, Asn, Leu, Lys, Phe, and Glu, which may serve as key interaction points for controlling this destructive plant pathogen. Additionally, ProTox-II analysis classified all synthesized compounds as toxicity class IV and confirmed that they satisfy Lipinski’s rule, suggesting their potential as effective agrochemical candidates. <b>Conclusions:</b> The synthesized spiro(DHPM-isatin) derivatives demonstrated significant nematicidal activity, with compound (<b>IVb</b>) emerging as the most potent, likely due to the presence of methoxy and amide functionalities. The combined <i>in vitro</i> and <i>in silico</i> findings support its potential as a safe and effective agrochemical candidate for the management of <i>M. incognita</i>.</p>

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Spiro(DHPM-isatin) Derivatives: Synthesis, Nematicidal Activity, and Computational Analysis

  • 期刊论文

  • 发表日期：

    2025年7月28日

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  • Jashandeep Kaur,
  • Divya Utreja,
  • N.K. Dhillon,
  • Rajesh K. Pathak,
  • Harwinder Singh Buttar

摘要

Abstract

Objective: Dihydropyrimidinone–isatin derivatives exhibit a wide range of biological activities, including antifungal, antibacterial, antitumor, and anticancer properties. Due to the deregistration of all existing antinemic compounds, our research group aims to identify new compounds with potent nematicidal activity. Methods: A one-pot nucleophilic addition of urea and a 1,3-dicarbonyl compound to the C-3 position of isatin was performed to obtain spiro(DHPM-isatin) derivatives. These were characterized using 1H, 13C NMR, FT-IR spectroscopy, and mass spectrometry. The synthesized derivatives were evaluated for their ovicidal and larvicidal potential against the plant pathogen Meloidogyne incognita. Results and Discussion: The spiro(DHPM-isatin) derivative (IVe) exhibited significant inhibition of egg hatching, achieving 98.00% inhibition at 1500 ppm after 168 h, along with notable larvicidal activity. In contrast, derivative (IVf) showed exceptional efficacy, causing 100% juvenile mortality at 168 h at concentrations of 750 ppm and above, along with pronounced inhibition of egg hatching. Furthermore, in silico studies conducted on five M. incognita proteins—carboxylic ester hydrolase, cytochrome c oxidase, putative aspartate protease, ATP synthase, and cytochrome b—revealed that the tested derivatives (IVa–IVh) effectively bind to the amino acid residues Tyr, Glu, Arg, His, Ala, Asp, Ser, Asn, Leu, Lys, Phe, and Glu, which may serve as key interaction points for controlling this destructive plant pathogen. Additionally, ProTox-II analysis classified all synthesized compounds as toxicity class IV and confirmed that they satisfy Lipinski’s rule, suggesting their potential as effective agrochemical candidates. Conclusions: The synthesized spiro(DHPM-isatin) derivatives demonstrated significant nematicidal activity, with compound (IVb) emerging as the most potent, likely due to the presence of methoxy and amide functionalities. The combined in vitro and in silico findings support its potential as a safe and effective agrochemical candidate for the management of M. incognita.