Synthesis, molecular modelling study of the methaqualone analogues as anti-convulsant agent with improved cognition activity and minimized neurotoxicity
2021; Elsevier BV; Volume: 1251; Linguagem: Inglês
10.1016/j.molstruc.2021.131972
ISSN1872-8014
AutoresIqrar Ahmad, Sazedur Rahman Akand, Matin Shaikh, Rahul Pawara, S Manjula, Harun Patel,
Tópico(s)Synthesis and pharmacology of benzodiazepine derivatives
ResumoIn the current research, methaqualone derivatives were synthesized and assessed for their anti-convulsant activity. Among them, compounds 3, 4, 6, 7 and 11 exhibited significant anti-convulsant activities with ED50 values of 132.23 mg/kg, 120.34 mg/kg, 100.78 mg/kg, 145.89 mg/kg, and 148.46 mg/kg, respectively. The toxicity profiling (TD50) of these compounds (3, 4, 6, 7 and 11) demonstrated that these drugs caused only a minor neurological impairment. The PI scores of these compounds (3, 4, 6, 7 and 11) were higher than the reference drug (methaqualone PI: 1.99). The acetylcholinesterase enzyme level is significantly reduced in these compounds, indicating the enhancement of cognition activity. Pharmacophoric modelling and molecular docking studies against the human GABA-A receptor are in close agreement with each other. Molecular dynamic simulation of compound 6 indicates that it remains stable with the human GABA-A receptor for a 100 ns time span.
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