Design, synthesis, molecular docking and pharmacological evaluation of novel triazine-based triazole derivatives as potential anticonvulsant agents

Abdulrahman G Alhamzani; Tarek A Yousef; Mortaga M Abou-Krisha; M S Raghu; K Yogesh Kumar; M K Prashanth; Byong-Hun Jeon

doi:10.1016/j.bmcl.2022.129042

Design, synthesis, molecular docking and pharmacological evaluation of novel triazine-based triazole derivatives as potential anticonvulsant agents

Bioorg Med Chem Lett. 2022 Dec 1:77:129042. doi: 10.1016/j.bmcl.2022.129042. Epub 2022 Nov 1.

Authors

Abdulrahman G Alhamzani¹, Tarek A Yousef², Mortaga M Abou-Krisha³, M S Raghu⁴, K Yogesh Kumar⁵, M K Prashanth⁶, Byong-Hun Jeon⁷

Affiliations

¹ College of Science, Chemistry Department, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi Arabia.
² College of Science, Chemistry Department, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi Arabia; Department of Toxic and Narcotic Drug, Forensic Medicine, Mansoura Laboratory, Medicolegal Organization, Ministry of Justice, Egypt.
³ College of Science, Chemistry Department, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi Arabia; Department of Chemistry, South Valley University, Qena 83523, Egypt.
⁴ Department of Chemistry, New Horizon College of Engineering, Bengaluru 560 103, India.
⁵ Department of Chemistry, Faculty of Engineering and Technology, Jain University, Ramanagara 562 112, India.
⁶ Department of Chemistry, B N M Institute of Technology, Bengaluru 560 070, India. Electronic address: prashanthmk87@gmail.com.
⁷ Department of Earth Resources and Environmental Engineering, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. Electronic address: bhjeon@hanyang.ac.kr.

PMID: 36332884
DOI: 10.1016/j.bmcl.2022.129042

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.

Keywords: Anticonvulsant; Drug-likeness; Molecular docking; Triazine; Triazole.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anticonvulsants* / chemistry
Anticonvulsants* / pharmacology
Anticonvulsants* / therapeutic use
Electroshock
Humans
Molecular Docking Simulation
Molecular Structure
Pentylenetetrazole
Seizures / chemically induced
Seizures / drug therapy
Structure-Activity Relationship
Triazines* / pharmacology
Triazoles

Substances

Anticonvulsants
Triazines
Pentylenetetrazole
Triazoles