Synthesis, computational analysis and antimicrobial and antifungal evaluation of a quinone substituted piperazine derivative

In the present study, a novel quinone-substituted piperazine compound (3) was synthesized and characterized using various spectroscopic techniques including FT-IR,1H NMR,13C NMR, UV-Vis, and MS analyses. The conformational preferences of compound (3) were investigated using the semi-empirical PM3 method, and the lowest-energy conformer was then optimized using the Density Functional Theory (DFT) at the wb97xd/6-311++G(d,p) level to determine its optimized structure. Molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO, LUMO) analyses were performed on the optimized structure using the same level of theory. Molecular docking studies revealed that compound (3) binds strongly to DNA and to Escherichia coli DNA gyrase B. Molecular dynamics (MD) simulations over 200 ns indicated that the (3)-DNA and (3)-6F86 complexes remained stable under the simulated conditions. These in silico results provide preliminary insights into the potential biological activities of compound (3), but experimental studies are needed to confirm these findings. The antibacterial and antifungal activities of (3) were evaluated using the disk diffusion method against various Gram-positive and Gram-negative bacterial strains, including Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, and Escherichia coli. The results showed that compound (3) exhibited greater antimicrobial activity than its precursor (1), particularly against Enterococcus faecalis and Micrococcus luteus. Additionally, (3) demonstrated significant antifungal activity against Aspergillus niger and Alternaria alternata.