Synthesis, characterization, antibacterial activity of thiosemicarbazones derivatives and their computational approaches: Quantum calculation, molecular docking, molecular dynamic, ADMET, QSAR.

The thiosemicarbazones and their derivatives have been recognized as antimicrobial agents against human pathogenic bacteria and fungi. Regarding these prospective, this study was designed to address the new antimicrobial agents from thiosemicarbazones and their derivatives. These derivatives were synthesized by multi-step synthesis methods, such as alkylation, acidification, esterification, and formed the 4-(4'-alkoxybenzoyloxy) thiosemicarbazones and its derivatives THS1, THS2, THS3, THS4, and THS5). Afterward the synthesis, compounds were characterized by H NMR, FTIR spectra, and melting point. Later, the computational tools were applied to evaluate the drug likeness properties, bioavailability score, Lipinski rule, absorption, distribution, metabolism, excretion, and toxicity (ADMET). Secondly, the quantum calculations, for instance HOMO, LUMO and chemical descriptors, were calculated by the density functional theory (DFT). Finally, the molecular docking was performed against seven human pathogenic bacteria, black fungus (Rhizomucor mieh, Mucor lusitanicus, Mycolicibacterium smegmatis) and white fungus strains (Candida Auris, Aspergillus luchuensis, Candida albicans). To check and validate of molecular docking procedure and stability of docked complex for ligand and protein, the molecular dynamic was performed of docked complex. From the docking score with calculating the binding affinity, these derivatives could show a higher affinity than standard drug against all pathogens. From the computational details, it could be decided to do test as antimicrobial activity against Staphylococcus aurious, Staphylococcus homonis, , and Shigella flexneria. The obtained result of antibacterial activity compared to standard drugs, and it was found that the synthesized compounds were almost same value of standard drug. Finally, it could be said from the and study that the thiosemicarbazones derivatives are good antimicrobial agents.