Design, Synthesis, and Preliminary Pharmacological Evaluation of Novel Thiazolidinone Derivatives As Potential Benzodiazepine Agonists

Overview

Journal Mol Divers

Date 2021 Jan 23

PMID 33484399

Citations 4

Authors

Ali Almasirad

Maryam Ghadimi

Saeideh Mirahmadi

Pouya Ahmadian Kodakan

Reza Jahani

Maryam Nazari

Elham Rezaee

Homa Azizian

Parmida Rabizadeh

Sayyed Abbas Tabatabai

Mehrdad Faizi

Affiliations

Soon will be listed here.

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. 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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