Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives

Abstract

A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1–24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100%) against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II). The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

Biological Activity of Quinazolinones

“…Compounds 50-53 were most potent with 100% protection against PTZ-induced convulsions compared with the reference drug sodium valproate. Abuelizz HA et al [72] synthesized a of 6,8-diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones analogues (54; R = Cl, Br, F) that revealed good anticonvulsant activity as evaluated by the maximal electroshock-induced seizure and subcutaneous pentylenetetrazole tests.…”

Ammonium Chloride Assisted Microwave Mediated Domino Multicomponent Reaction: An Efficient and Sustainable Synthesis of Quinazolin‐4(3H)‐imines under Solvent Free Condition

“…Taking into account the broad biological activities quinazolinimies display such as potent EGFR inhibitors, antimalarial, antitumoractivity, anticonvulsive, antimicrobial, anti‐viral anticholinesterase, anti‐inflammatory and COX‐II inhibitors, and α‐glucosidase inhibitors, several synthetic strategies for the synthesis of these moieties have been developed. Some of the notable methods are listed herewith.…”

Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents

“…Epilepsy is a serious and common neurological condition which is characterized by seizures due to hyper synchronous discharges in the brain . According to an epidemiological study, epilepsy is the third most destructive neurological disorder, affecting more than 50 million people worldwide with almost 90% of these patients being in developing countries .…”