Integration of In-vivo screening, molecular docking, and molecular dynamics simulations for studying the antiepileptic potential of newly synthesized 5-naphthalen-1-yl-5,10-dihydro-1 H -pyrimido[4,5-b]quinoline-2,4-diones in optimized reaction conditions by utilizing l -proline as green catalyst

In a green, one-pot approach, several 5-naphthalen-1-yl-5,10-dihydro-1 H -pyrimidoi-[4,5-b]-iquinoline-2,4-dionesi (4a-k) were synthesized via a three-component reaction comprising substituted anilines, naphthaldehyde, and barbituric acids. The reaction conditions were optimized by testing different catalysts (PTSA, CF 3 COOH, and l-proline ) and different solvents. Most of the tested reaction conditions influenced the synthetic reaction. l-proline was more effective with water as a solvent in synthesizing the targeted compounds with high yields. All the synthesized compounds underwent antiepileptic screening using in vivo and in silico methods. In vivo, screening has been performed following the maximal electroshock seizure (MES), and subcutaneous pentylenetetrazole (scPTZ) animal screening methods. The antidepressant screening of the most potent antiepileptic compounds has been tested through a locomotor impairment test (using an actophotometer). The in silico molecular docking and simulation studies were determined by utilizing AutoDock 4.2 version and Groomacs. Among all, compounds 4b, 4d, 4e, and 4j have demonstrated significant antiepileptic activity with effective antidepressant properties. In silico studies (calculation of ADME parameters, molecular docking, and MD simulation) established that targeted molecules have good ADME parameters (good for oral use), the possible mechanism involved interactions primarily with GABA A receptors while interactions with other receptors like VGSCs and NMDA also took place.