Two- and Three-Directional Synthesis by 3-7MCRs of Novel (Imidazolidine/Thiazolidine)-2,4-Diones: Characterization, Antibacterial, Anticonvulsant and Molecular Docking Investigation

Abstract

AbstractA variety of new compounds containing two or three biologically active nuclei of imidazolidine-2,4-dione and thiazolidine-2,4-dione (TZD) via optimization two and three directional 3 and 4MCRs Knoevenagel condensation (method A) and two and three directional 5 and 7 MCRs Bucherer-Bergs (method B). The structure of these derivatives was confirmed by FT-IR,1HNMR,13CNMR, and Elemental analysis. To evaluate the anticonvulsant activity of these derivatives, all the compounds were subjected to molecular docking studies for Anticonvulsant Drug Binding (ADB) to the Voltage-Gated Sodium Channel Inner Pore (VGCIP). The in silico molecular docking study results showed that molecules5c,9,7, and10among the synthesized compounds have the lowest docking score which shows the highest combined desire for the channel and have a good affinity toward the active pocket, thus, they may be considered good anticonvulsant agents. Also, to evaluate the antibacterial properties of these derivatives, they underwent molecular docking studies with four bacterial proteins. Gram-positive bacteria such asB. anthracis(PDB ID: 3TYE) andS. aureus(PDB ID: 3ACX) and gram-negative bacteriaE. coli(PDB ID: 1AB4) andP. aeruginosa(PDB ID: 5U39). The most significant overall score has been obtained forS. aureus(PDB ID: 3ACX) bacteria. A combination of10displays strong antibacterial activity against two gram-positive bacterial and compounds4aand7with gram-negative proteins bacterial. The highest binding affinity is related to compound7for gram-negativeP. aeruginosa(PDB ID: 5U39) bacterial proteins. The antibacterial properties of these derivatives were as well experimentally investigated.