A facile synthesis of 1,3,4-oxadiazole-based carbamothioate molecules: Antiseizure potential, EEG evaluation and in-silico docking studies

Rasool, Nasır; Razzaq, Zainib; Khan, Samreen Gul; Javaid, Sana; Akhtar, Naheed; Mahmood, Sadaf; Christensen, Jørn B.; Altaf, Ataf Ali; Anjum, Syed Muhammad Muneeb; Alqahtani, Faleh; Alasmari, Abdullah F.; Imran, Imran

doi:10.1016/j.arabjc.2023.104610

Cited by 8 publications

(4 citation statements)

References 51 publications

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“…PTZ is a chemoconvulsant that interrupts GABAergic neurotransmission, and its repetitive administration causes increased seizure susceptibility in laboratory animals. 42 In the present study, it was noted that animals pretreated with diazepam remained free from behavioral progression to seizures of higher severity and associated electrographic alterations. Diazepam belongs to benzodiazepines and is known to reduce neuronal excitation by increasing the binding of GABA with the GABA-A receptor, leading to prolonged opening of associated chloride channels.…”

Section: Discussionsupporting

confidence: 52%

“…The current study evaluates the impact of combining brivaracetam with a novel AMPA-antagonizing antiseizure drug, perampanel, on seizure progression in the PTZ-induced kindling model. PTZ is a chemoconvulsant that interrupts GABAergic neurotransmission, and its repetitive administration causes increased seizure susceptibility in laboratory animals . In the present study, it was noted that animals pretreated with diazepam remained free from behavioral progression to seizures of higher severity and associated electrographic alterations.…”

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: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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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“…Compound 3b showed the best binding energy of −3.68 against SV2A ( Figure 7) and −6.64 against 6HUP (Figure 8). [ 18 ]…”

Section: Overview Of the Diverse Derivatives And Their Activitiesmentioning

confidence: 99%

“…Compound 3b showed the best binding energy of −3.68 against SV2A (Figure 7) and −6.64 against 6HUP (Figure 8). [18] Wang et al reported three series of compounds and their anticonvulsant activity assessed by in vivo MES and subcutaneous pentylenetetrazol (SC PTZ) models. Neurotoxicity studies of all test compounds were also performed using the rotating rod (ROT) method.…”

mentioning

confidence: 99%

Unveiling the chemistry of 1,3,4‐oxadiazoles and thiadiazols: A comprehensive review

Gour,

Yahya,

Shahar Yar

2023

Archiv der Pharmazie

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Oxadiazoles and thiadiazoles are malleable heterocycles that have recently generated major interest in the field of medicinal chemistry. Compounds based on these moieties have versatile biological applications such as anticonvulsant, anticancer, antidiabetic, and antioxidant agents. Due to the versatile nature and stability of the oxadiazole and thiadiazole nucleus, medicinal chemists have changed the structural elements of the ring in numerous ways. These compounds have shown significant anticonvulsant effects, demonstrating their potential in the management of epileptic disorders. In this review, we have covered numerous biological pathways and in silico targeted proteins of oxadiazole and thiadiazole derivatives for treating various biological disorders. The data compiled in this article will be helpful for researchers, research scientists, and research chemists who work in the field of drug discovery and drug development.

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Recent chemistry and applications of 1,3,4-oxadiazoles

Gorbunov,

Fershtat

2024

Advances in Heterocyclic Chemistry

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A facile synthesis of 1,3,4-oxadiazole-based carbamothioate molecules: Antiseizure potential, EEG evaluation and in-silico docking studies

Cited by 8 publications

References 51 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

Unveiling the chemistry of 1,3,4‐oxadiazoles and thiadiazols: A comprehensive review

Recent chemistry and applications of 1,3,4-oxadiazoles

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