| Abstrakt: |
A variety of new compounds containing two or three biologically active imidazolidine-2,4-dione and thiazolidine-2,4-dione (TZD) cores through two- and three-way optimization of 3 and 4CR by Knoevenagel condensation were synthesized (Method A). In another attempt, two and three Bucherer–Berg modified with 5 and 7CR directed to synthesize larger homologous molecules were used (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 considered to be studied through molecular docking for Anticonvulsant Drug Binding (ADB) to the Voltage-Gated Sodium Channel Inner Pore (VGCIP). The in-silico molecular docking study results showed that molecules 5c, 7, 9, and 10 among the synthesized compounds with − 8.31, − 9.23, − 8.91, and − 10.79 kJ mol−1 glide scores respectively, lead to more binding affinity toward the channel and fitting well in the active pocket, thus, they may be considered as good anticonvulsant agents. Also, to evaluate the antibacterial properties of these derivatives, the ligand–protein molecular docking calculation using the active sites of the following bacterial proteins has been performed. Gram-positive bacteria such as B. anthracis (PDB ID: 3TYE) and S. aureus (PDB ID: 3ACX) and gram-negative bacteria E. coli (PDB ID: 1AB4) and P. aeruginosa (PDB ID: 5U39). The most significant overall score has been obtained for S. aureus (PDB ID: 3ACX) bacteria. According to the calculation compound 10 leads to the most efficient antibacterial activity against two Gram-positive bacteria and compounds 4a and 7 with Gram-negative proteins bacterial. The highest binding affinity is related to compound 7 for the Gram-negative P. aeruginosa (PDB ID: 5U39) protein target. The antibacterial properties of these derivatives were also experimentally investigated confirming the results obtained by the ligand–protein molecular docking calculation. [ABSTRACT FROM AUTHOR] |
