Design, synthesis and biological evaluation of naphthalene-derived (arylalkyl)azoles containing heterocyclic linkers as new anticonvulsants: A comprehensive in silico, in vitro, and in vivo study was written by Valipour, Mehdi;Naderi, Nima;Heidarli, Elmira;Shaki, Fatemeh;Motafeghi, Farzaneh;Talebpour Amiri, Fereshteh;Emami, Saeed;Irannejad, Hamid. And the article was included in European Journal of Pharmaceutical Sciences in 2021.Name: 1-Methylbenzimidazole This article mentions the following:
In continuation of our research to find strong and safe anticonvulsant agents, a number of (arylalkyl)azoles (AAAs) containing naphthylthiazole and naphthyloxazole scaffolds were designed and synthesized. The in vivo anticonvulsant evaluations in BALB/c mice revealed that some of them had significant anticonvulsant activity in both maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy. The best profile of activity was observed with compounds containing imidazole and triazole rings (C1, C6, G1, and G6). In particular, imidazolylmethyl-thiazole C1 with median ED (ED50)= 7.9 mg/kg in the MES test, ED50= 27.9 mg/kg in PTZ test, and without any sign of neurotoxicity (in the rotarod test, 100 mg/kg) was the most promising compound The patch-clamp recording was performed to study the mechanism of action of the representative compound C1 on hippocampal dentate gyrus (DG) cells. The results did not confirm any modulatory effect of C1 on the voltage-gated ion channels (VGICs) or GABAA agonism, but suggested a significant reduction of excitatory postsynaptic currents (EPSCs) frequency on hippocampal DG neurons. Sub-acute toxicity studies revealed that administration of the most active compounds (C1, C6, G1, and G6) at 100 mg/kg bw/day for two weeks did not result in any mortality or significant toxicity as evaluated by assessment of biochem. markers such as lipid peroxidation, intracellular glutathione, total antioxidant capacity, histopathol. changes, and mitochondrial functions. Other pharmacol. aspects of compounds including mechanistic and ADME properties were investigated computationally and/or exptl. Mol. docking on the NMDA and AMPA targets suggested that the introduction of the heterocyclic ring in the middle of AAAs significantly affects the affinity of the compounds The obtained results totally demonstrated that the prototype compound C1 can be considered as a new lead for the development of anticonvulsant agents. In the experiment, the researchers used many compounds, for example, 1-Methylbenzimidazole (cas: 1632-83-3Name: 1-Methylbenzimidazole).
1-Methylbenzimidazole (cas: 1632-83-3) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole is incorporated into many important biological compounds. The most pervasive is the amino acid histidine, which has an imidazole side-chain. Histidine is present in many proteins and enzymes, e.g. by binding metal cofactors, as seen in hemoglobin.Name: 1-Methylbenzimidazole
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem