Design, synthesis, molecular docking and pharmacological evaluation of novel triazine-based triazole derivatives as potential anticonvulsant agents. (1st December 2022)

• Record Type: Journal Article
• Authors: Alhamzani, Abdulrahman G.; Yousef, Tarek A.; Abou-Krisha, Mortaga M.; Raghu, M.S.; Yogesh Kumar, K.; Prashanth, M.K.; Jeon, Byong-Hun
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 77(2022)
• Publication Date: 2022-12-01
• Subjects: Triazine -- Triazole -- Anticonvulsant -- Molecular docking -- Drug-likeness; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2022.129042
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: A series of novel triazine-linked triazole derivatives (4a-j) were synthesized. The novel compounds were evaluated as anticonvulsant agents against MES and PTZ model. Some compounds showed more PI values than that of methaqualone and valproate. Molecular docking studies were carried out to explore the binding interaction of the most active compounds. The experimental results were supported by the molecular docking studies. Abstract: Triazine-linked triazole compounds (4a-j ) were designed, synthesized, and then examined for their anticonvulsant abilities. Compounds 4e, 4f, 4g, 4i, and 4j displayed significant anticonvulsant activity in both maximum electroshock seizure (MES) and pentylenetetrazole (PTZ) induced seizure during the preliminary screening. The phase II anticonvulsant activity statistics revealed that compounds 4e, 4f, 4g, 4i, and 4j demonstrated excellent activity as compared to the conventional drugs methaqualone and valproate, supporting the potential of these triazine-linked triazole analogues as novel anticonvulsant agents. To take use of the findings, computational parameters including docking analysis and drug-likeness prediction were carried out. Molecular modelling studies supported the essential pharmacophoric information that the structure activity relationship offered. The triazine-linked triazole analogues that were investigated might be viewed as helpful models for future research and derivatization.