Browsing by Author "Ravi Bhushan Singh"

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Design, synthesis, characterization, and molecular modeling studies of novel oxadiazole derivatives of nipecotic acid as potential anticonvulsant and antidepressant agents
(Birkhauser Boston, 2018) Ravi Bhushan Singh; Gireesh Kumar Singh; Krishna Chaturvedi; Devendra Kumar; Sushil Kumar Singh; Md. Kamaruz Zaman
A series of fifteen novel nipecotic acid 1,3,4-oxadiazole hybrids were synthesized with the intent to improve the lipophilicity of nipecotic acid and its penetration through the blood—brain barrier (BBB). The structures of the compounds were established by FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. The effect of the synthesized compounds was assessed on motor coordination using the rotarod test in mice. Anticonvulsant activity was evaluated using the subcutaneous pentylenetetrazol (scPTZ) test in mice. Five compounds (5d, 5e, 5g, 5m, and 5o) exhibited significant protection against scPTZ-induced seizures. None of the compounds produced any disruption in motor coordination as observed in the rota-rod test, nor did they elevate the serum levels of biochemical markers related to hepatic and renal toxicity, affirming their relative safety. The derivatives also exhibited significant antidepressant activity, devoid of serotonergic augmentation as assessed using the despair swim test, 5-hydroxytryptophan (5-HTP)-induced head twitch test and learned helplessness test. In in silico docking studies on a homology model on target GABA transporter 1 (GAT1) protein and the most active compound 5e helped to identify critical enzyme-ligand interactions leading to the inhibition of the GAT1 transporter. © 2017, Springer Science+Business Media, LLC.
Virtual screening study to identify GSK-3β inhibitors: A combined ligand-based and structure-based drug discovery approach
(National Institute of Science Communication and Policy Research, 2025) Anuj Kumar Mishra; Ravi Prakash Singh; Ankit Ganeshpurkar; Gireesh Kumar Singh; Pankaj Agrawal; Sushil K. Singh; Ravi Bhushan Singh
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting millions worldwide. While its aetiology is complex, a central role is attributed to the dysregulation of amyloid-beta (Aβ) protein homeostasis. Emerging evidence supports the involvement of glycogen synthase kinase-3β (GSK-3β) in AD pathogenesis through its influence on Aβ production and accumulation. Inhibiting GSK-3β is considered a promising therapeutic strategy to mitigate Aβ-related neurotoxicity. This study employed ligand-based drug design and computational modelling to identify novel GSK-3β inhibitors. Leveraging the pharmacophore of the known inhibitor CX-4945, a virtual screening campaign was conducted against the Molport database. The resulting hits were subjected to rigorous filtering based on drug-likeness and PAINS criteria. Subsequent docking and molecular dynamics simulations identified MolPort-002-524-637 and MolPort-006-387-505 as promising candidates. These compounds exhibited superior binding affinities compared to CX-4945 and displayed favourable in silico ADME/Tox properties. © 2025, National Institute of Science Communication and Policy Research. All rights reserved.