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Design, synthesis, and preliminary pharmacological evaluation of novel thiazolidinone derivatives as potential benzodiazepine agonists

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Abstract

Thiazolidinones are well-known heterocycles that demonstrate promising biological effects such as anticonvulsant activity. Hybridization of these chemicals with scaffold, which has necessary pharmacophores for binding to the benzodiazepine receptors, can prompt a novel structure possessing extensive anticonvulsant effects. In this study, novel derivatives of thiazolidinone as new benzodiazepine agonists were designed, synthesized, and biologically evaluated. Compound 5h, 4-chloro-2-(2-fluorophenoxy)-N-(4-oxo-2-(p-tolyl)thiazolidin-3-yl)benzamide, exhibited considerable anticonvulsant activity, proper sedative–hypnotic effect, no memory impairment, and no muscle relaxant effect. The pharmacological effects of the designed compounds were antagonized by flumazenil, which confirmed the benzodiazepine receptors’ involvement in their biological effects. Based on in silico calculations of ADME properties of our novel compounds, they could be active oral agents potentially.

Graphic abstract

In this study, we designed novel structures by the hybridization of thiazolidinone moiety with scaffold which has necessary pharmacophores for binding to the benzodiazepine receptors. The results are very promising for developing new lead compounds as benzodiazepine agonists possess anticonvulsant effects.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Ali Almasirad, Maryam Ghadimi, Saeideh Mirahmadi & Parmida Rabizadeh

  2. Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, No.2660, Vali-E-Asr., 1991953381, Tehran, Iran

    Pouya Ahmadian Kodakan, Reza Jahani & Mehrdad Faizi

  3. Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Maryam Nazari, Elham Rezaee & Sayyed Abbas Tabatabai

  4. Department of Medicinal Chemistry, Pharmacy School, International Vice Chancellor Office, Iran University of Medical Sciences, Tehran, Iran

    Homa Azizian

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  1. Ali Almasirad
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Almasirad, A., Ghadimi, M., Mirahmadi, S. et al. Design, synthesis, and preliminary pharmacological evaluation of novel thiazolidinone derivatives as potential benzodiazepine agonists. Mol Divers 26, 769–780 (2022). https://doi.org/10.1007/s11030-021-10182-x

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  • DOI: https://doi.org/10.1007/s11030-021-10182-x

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