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 1H 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 in-vitro test as antimicrobial activity against Staphylococcus aurious, Staphylococcus homonis, Salmonella typhi, 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 in-vitro and in-silico study that the thiosemicarbazones derivatives are good antimicrobial agents.

Effects of temperature and polyols on the ciprofloxacin hydrochloride-mediated micellization of sodium dodecyl sulfate.

Herein, a conductivity method was engaged to explore the effects of a fluoroquinolone drug, namely ciprofloxacin hydrochloride (CFH)/CFH + polyols (organic compounds with multiple hydroxyl groups (glucose and fructose)), on the aggregation phenomenon of sodium dodecyl sulfate (SDS) at different temperatures (298.15-318.15 K) while maintaining a gap of 5 K. In this study, the critical micelle concentration (cmc) of the SDS/SDS + CFH mixture in water and polyols media was determined from plots of the specific conductivity versus the concentration of SDS to gain knowledge of the effects of CFH/CFH + polyols on the micelle formation behavior of SDS. The cmc value of the surfactant decreases in the presence of CFH in an aqueous medium; thus, CFH favors the micellization of SDS. The cmc values of SDS and the SDS + CFH mixture were enhanced in polyols media. The cmc values of SDS/SDS + CFH show a U-shaped behavior with temperature. The counterion dissociation (α) of the pure surfactant is higher in the presence of the drug and is further enhanced through an increase in the CFH concentration in water/polyols media. Different thermodynamic parameters, such as the Gibbs free energy of micellization , standard enthalpy , entropy , different transfer energies and enthalpy-entropy compensation parameters of micellization were determined and illustrated in detail to compare these parameters between the pure SDS and SDS + CFH mixture in polyols media. The negative values of for the SDS/SDS + CFH mixture in all cases indicate spontaneous micelle formation. The and values indicate the presence of both hydrophobic and electrostatic interactions amongst the studied components.