Novel 4-thiazolidinone derivatives as agonists of benzodiazepine receptors: design, synthesis and pharmacological evaluation

Faizi, Mehrdad; Jahani, Reza; Ebadi, Seyed Abbas; Tabatabai, Sayyed Abbas; Rezaee, Elham; Lotfaliei, Mehrnaz; Amini, Mohsen; Almasirad, Ali

doi:10.17179/excli2016-692

Cited by 12 publications

(5 citation statements)

References 19 publications

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“…A previous study by Faizi et al reported the high effectivity of diazepam against PTZ as the ED 50 of diazepam was very low, i.e., 0.96 mg/kg in mice exposed to a lethal dose of PTZ (100 mg/kg). 45 The pretreatment of mice with brivaracetam alone at 10 mg/ kg caused a delay in initiation and progression to PTZ-induced seizures to convulsions of higher severity, and the difference was noteworthy after the ninth PTZ injection. 46 However, when the dose of brivaracetam was doubled to 20 mg/kg, earlier protection from the kindling process was notable after the fifth PTZ injection, but the EEGs recorded in electrodebearing mice demonstrated the frequently occurring spikes of higher amplitude.…”

Section: Discussionmentioning

confidence: 98%

“…The drugs when used alone worked less effectively in preventing the seizures as compared to diazepam, and it might be due to the mechanism of action of diazepam as it directly prevents the GABA-antagonizing effects of PTZ. A previous study by Faizi et al reported the high effectivity of diazepam against PTZ as the ED 50 of diazepam was very low, i.e., 0.96 mg/kg in mice exposed to a lethal dose of PTZ (100 mg/kg) …”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice

Farooq,

Javaid,

Ashraf

et al. 2024

ACS Omega

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Pentylenetetrazole (PTZ)-induced kindling is a broadly used experimental model to study the anticonvulsive potential of new and existing chemical moieties with the aim of discovering drugs hindering seizure progression and associated neurological comorbidities. In the present study, the impact of brivaracetam (BRV) (10 and 20 mg/kg) as monotherapy as well as in combination with 0.25 mg/kg of perampanel (PRP) was investigated on seizure progression with simultaneous electroencephalographic changes in PTZ kindling mouse model. Subsequently, mice were experimentally analyzed for anxiety, cognition, and depression after which their brains were biochemically evaluated for oxidative stress. The outcomes demonstrated that BRV alone delayed the kindling process, but BRV + PRP combination significantly (p < 0.0001) protected the mice from seizures of higher severity and demonstrated an antikindling effect. The PTZ-kindled mice exhibited anxiety, memory impairment, and depression in behavioral tests, which were remarkably less (p < 0.001) in animals treated with drug combination (in a dose-dependent manner) as these mice explored central, illuminated, and exposed zones of open-field test, light/dark box, and elevated plus maze. Moreover, memory impairment was demonstrated by kindled mice, which was significantly (p < 0.001) protected by BRV + PRP as animal's spontaneous alteration, object discrimination, and step-through latencies were increased in various tests employed for the assessment of cognitive abilities. The brains of PTZkindled mice had increased malondialdehyde and reduced antioxidant enzymes while treatment with BRV + PRP combination prevented kindling-induced elevation in oxidative markers. The outcomes of this study demonstrate that combining the PRP at low dose augmented the antiseizure properties of BRV as both drugs when administered simultaneously hindered the process of kindling by reducing PTZ-induced excessive electrical activity and oxidative stress in the brain.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

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Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice

Farooq,

Javaid,

Ashraf

et al. 2024

ACS Omega

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“…62 Drug candidates showing violation of more than one of these rules will lead to difficulty in oral absorption. 63 Using the AdmetSAR/Pro Tox II Web server tools, the synthesized compounds' organ toxicity profiles, ligand toxicological endpoints, and LD 50 were predicted. 64 Oral bioavailability is accounted as a crucial characteristic for the discovery of efficacious medicinal drugs.…”

Section: In Silico Computational Studies Prediction Of Drug-likeness ...mentioning

confidence: 99%

Ultrasonic-Assisted Synthesis of Heterocyclic Curcumin Analogs as Antidiabetic, Antibacterial, and Antioxidant Agents Combined with in vitro and in silico Studies

Zelelew¹,

Endale²,

Melaku³

et al. 2023

AABC

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Background Heterocyclic analogs of curcumin have a wide range of therapeutic potential and the ability to control the activity of a variety of metabolic enzymes. Methods 1 H-NMR and 13 C-NMR spectroscopic techniques were used to determine the structures of synthesized compounds. The agar disc diffusion method and α-amylase inhibition assay were used to examine the antibacterial and anti-diabetic potential of the compounds against α-amylase enzyme inhibitory activity, respectively. DPPH-free radical scavenging and lipid peroxidation inhibition assays were used to assess the in vitro antioxidant potential. Results and Discussion In this work, nine heterocyclic analogs derived from curcumin precursors under ultrasonic irradiation were synthesized in excellent yields (81.4–93.7%) with improved reaction time. Results of antibacterial activities revealed that compounds 8, and 11 displayed mean inhibition zone of 13.00±0.57, and 19.66±00 mm, respectively, compared to amoxicillin (12.87±1.41 mm) at 500 μg/mL against E. coli , while compounds 8, 11 and 16 displayed mean inhibition zone of 17.67±0.57, 14.33±0.57 and 23.33±00 mm, respectively, compared to amoxicillin (13.75±1.83 mm) at 500 μg/mL against P. aeruginosa . Compound 11 displayed a mean inhibition zone of 11.33±0.57 mm compared to amoxicillin (10.75±1.83 mm) at 500 μg/mL against S. aureus . Compound 11 displayed higher binding affinities of −7.5 and −8.3 Kcal/mol with penicillin-binding proteins (PBPs) and β -lactamases producing bacterial strains, compared to amoxicillin (−7.2 and −7.9 Kcal/mol, respectively), these results are in good agreement with the in vitro antibacterial activities. In vitro antidiabetic potential on α -amylase enzyme revealed that compounds 11 (IC 50 =7.59 µg/mL) and 16 (IC 50 =4.08 µg/mL) have higher inhibitory activities than acarbose (IC 50 =8.0 µg/mL). Compound 8 showed promising antioxidant inhibition efficacy of DPPH (IC 50 = 2.44 g/mL) compared to ascorbic acid (IC 50 =1.24 g/mL), while compound 16 revealed 89.9±20.42% inhibition of peroxide generation showing its potential in reducing the development of lipid peroxides. In silico molecular docking analysis, results are in good agreement with in vitro biological activity. In silico ADMET profiles suggested the adequate oral drug-likeness potential of the compounds without adverse effects. Conclusion According to our findings, both biological activities and in silico computational studies results demonstrated that compounds 8, 11, and 16 are promising α -amylase inhibitors and antibacterial agents against E. coli , ...

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“…Thiazolidinone ring is a promising pharmacophore that has possessed a broad spectrum of pharmacological actions such as antimicrobial (compound A) (Fig. 1 ) [ 3 – 5 ], antiviral [ 6 ], antiparasitic [ 7 , 8 ], analgesic, anti-inflammatory [ 9 ], antioxidant [ 10 ], anticancer [ 6 , 7 , 11 ], antidiabetic [ 12 ], antihypertensive, anti-hyperlipidemic, anti-arrhythmic [ 13 ], anti-convulsant activities [ 14 , 15 ]. In the last two decades, 4-thiazolidinone pharmacophore has received great attention for its inhibitory effect on MurB and various substituted 4-thiazolidinones were explored for their antibacterial activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives as anti-MRSA and anti-H. pylori agents

et al. 2022

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In this work, we have synthesized twenty five new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives bearing an aryl or heteroaryl methylene group on position 5 of thiazolidinone and evaluated their antimicrobial activity against Gram-positive and -negative bacteria as well as three metronidazole resistant Helicobacter pylori strains. Most of the compounds were very potent towards tested Gram-positive bacteria and showed an antibacterial efficacy substantially greater than ampicillin as the reference drug. However, no effectiveness was observed for the Gram-negative microorganisms. The compounds 9, 20 and 29 exhibited strong antimicrobial activity against Helicobacter pylori strains (inhibition zone > 30 mm) in 100 μg/disc and (inhibition zone > 20 mm) in 50 μg/disc. Taking these findings together, it seems that these potent antibacterial derivatives could be considered as promising agents for developing new anti-infectious drugs against microorganisms resistant to currently available antibiotics. Graphical Abstract

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Novel 4-thiazolidinone derivatives as agonists of benzodiazepine receptors: design, synthesis and pharmacological evaluation

Cited by 12 publications

References 19 publications

Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice

Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice

Ultrasonic-Assisted Synthesis of Heterocyclic Curcumin Analogs as Antidiabetic, Antibacterial, and Antioxidant Agents Combined with in vitro and in silico Studies

Synthesis of new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives as anti-MRSA and anti-H. pylori agents

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