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2000
Volume 12, Issue 3
  • ISSN: 2213-3372
  • E-ISSN: 2213-3380

Abstract

Background

Heterocyclic compounds emerged promising choice in drug discovery and clinical research. Among various heterocycles, 5-aryl-1,2,4-triazolidine-3-thione and 1,2,4-triazospiro-3-thione derivatives also showed important biological applications. Hence, organic chemists are striving to develop various catalytic routes for the construction of these derivatives.

Methods

The present work describes the eco-friendly synthesis of 5-aryl-1,2,4-triazolidine-3-thione (3a-o) and 1,2,4-triazospiro-3-thione (5p-u) one-pot Multi-Component Reactions (MCRs) of substituted aromatic/heteroaromatic aldehyde, isatine and thiosemicarbazide in the presence of organocatalysts Glutamic acid (Glu) under microwave irradiation. Additionally, the homogeneity of the selected compounds was confirmed through various spectroscopic techniques such as FT-IR, 1H- 13C-NMR, and LC-MS. Further, the drug-likeness was evaluated using SwissADME software and the anti-microbial activity of the selected derivatives were tested.

Results

The reaction exhibits good tolerance towards various substituted aromatic/heteroaromatic aldehydes, isatine, and thiosemicarbazide, resulting in high yields of product isolation (86–92%). The computational ADME properties of the prepared derivatives were evaluated for their drug-like properties, along with an assessment of Lipinski’s Rule of Five. Selected derivatives were also tested for their antimicrobial properties, showing comparable activities.

Conclusion

Overall, this work describes a greener method synthesis of 5-aryl-1,2,4-triazolidine-3-thione derivatives (3a-o) and 1,2,4-triazospiro-3-thione derivatives (-). The catalysts used are biodegradable, environmentally friendly organocatalysts that align with green chemistry principles. The reaction is accelerated by microwave irradiation in the presence of ethanol. The developed method is simple, allowing for easy separation of the catalyst using hot ethanol and enabling recycling up to three times without affecting product isolation. The developed protocol offers advantages such as accessibility, cost-effectiveness, rapid reactions, mild atom economy, and elimination of hazardous solvents and catalysts usage. Selected derivatives were screened for antimicrobial activity, evaluated computationally for drug-likeness , and adhered to Lipinski’s rule of five.

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2025-03-24
2025-09-27

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Organocatalyzed Synthesis of 5-aryl-1,2,4-triazolidine-3-thione and 1,2, 4-triazospiro-3-thione, Drug-Likeness and Anti-Microbial Studies
Curr. Organocatal. 12, 177 (2025); https://doi.org/10.2174/0122133372352532250312043517
/content/journals/cocat/10.2174/0122133372352532250312043517
/content/journals/cocat/10.2174/0122133372352532250312043517
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  • Article Type:     Research Article
Keyword(s): anti-microbial; biodegradable; Glutamic acid; green chemistry; pharmacological; thiosemicarbazide

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