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Background <p>Since its first synthesis in the nineteenth century, hydantoin has emerged as a vital scaffold in drug development, especially for anticonvulsant, antimicrobial, antitumor, and anti-inflammatory agents. Phenytoin, a well-known hydantoin derivative, remains a cornerstone in epilepsy treatment due to its modulation of voltage-gated sodium channels. Beyond this, hydantoin derivatives exhibit diverse biological activities, including anticancer, immunomodulatory, and antimicrobial properties. Synthetic versatility and a broad bioactive profile enhance their pharmaceutical significance.</p> Objective <p>The objective of this review is to provide a comprehensive insights on hydantoin derivatives, highlighting their pharmacological potential, structural diversity, and synthetic approaches. It also explores how substitution patterns and stereochemistry influence their biological activity.</p> Materials and Methods <p>Hydantoin derivatives can be synthesized through conventional methods and advanced techniques, such as microwave-assisted synthesis. Their anticonvulsant properties are typically evaluated using both in vitro and in vivo models. Common in vivo screening includes intraperitoneal administration in maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ)-induced seizure models.</p> Results <p>Studies show that substitution at key positions on the hydantoin ring significantly affects biological activity. Microwave-assisted synthesis often yields more potent derivatives. Some compounds also exhibit anti-inflammatory and anticancer activities, broadening their therapeutic potential.</p> Conclusion <p>Hydantoin derivatives exhibit significant pharmacological potential, driven by their structural versatility and diverse substitution patterns. Enhanced synthetic approaches, such as microwave-assisted methods, improve yield and bioactivity. Their broad spectrum of action, particularly in anticonvulsant, anti-inflammatory, and anticancer domains, underscores their continued relevance in drug development.</p> Graphical Abstract <p></p>

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Exploring hydantoin frameworks: synthetic approaches and therapeutic potential

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月30日

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  • Nirmala V. Shinde,
  • Vrushali P. Patole,
  • Manoj R. Kumbhare,
  • Harsha Narkhede,
  • Ashwini T. Satalkar,
  • Anushka V. Thube,
  • Sachin K. Bhosale

摘要

Background

Since its first synthesis in the nineteenth century, hydantoin has emerged as a vital scaffold in drug development, especially for anticonvulsant, antimicrobial, antitumor, and anti-inflammatory agents. Phenytoin, a well-known hydantoin derivative, remains a cornerstone in epilepsy treatment due to its modulation of voltage-gated sodium channels. Beyond this, hydantoin derivatives exhibit diverse biological activities, including anticancer, immunomodulatory, and antimicrobial properties. Synthetic versatility and a broad bioactive profile enhance their pharmaceutical significance.

Objective

The objective of this review is to provide a comprehensive insights on hydantoin derivatives, highlighting their pharmacological potential, structural diversity, and synthetic approaches. It also explores how substitution patterns and stereochemistry influence their biological activity.

Materials and Methods

Hydantoin derivatives can be synthesized through conventional methods and advanced techniques, such as microwave-assisted synthesis. Their anticonvulsant properties are typically evaluated using both in vitro and in vivo models. Common in vivo screening includes intraperitoneal administration in maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ)-induced seizure models.

Results

Studies show that substitution at key positions on the hydantoin ring significantly affects biological activity. Microwave-assisted synthesis often yields more potent derivatives. Some compounds also exhibit anti-inflammatory and anticancer activities, broadening their therapeutic potential.

Conclusion

Hydantoin derivatives exhibit significant pharmacological potential, driven by their structural versatility and diverse substitution patterns. Enhanced synthetic approaches, such as microwave-assisted methods, improve yield and bioactivity. Their broad spectrum of action, particularly in anticonvulsant, anti-inflammatory, and anticancer domains, underscores their continued relevance in drug development.

Graphical Abstract