Salicylaldehyde-based Schiff Bases
Description
The escalating resistance to antimicrobial drugs has emerged as a critical public health concern, presenting formidable challenges to the effective treatment and control of bacterial infections. This alarming trend underscores the urgent need for the development of novel antimicrobial agents capable of combating resistant pathogens. In this context, Schiff bases, a class of compounds characterized by the presence of a functional group containing a nitrogen atom connected to an aryl or alkyl group, have garnered considerable attention due to their diverse biological activities, including antimicrobial, antiviral, and antimalarial properties. Recognizing the therapeutic potential of Schiff bases, we embarked on a study aimed at the synthesis and evaluation of salicylaldehyde-based Schiff base derivatives. The synthesized series comprised seventeen novel compounds, each structurally unique yet sharing a common scaffold that facilitated their biological activity. The chemical structures of these compounds were meticulously characterized using advanced spectroscopic techniques, including ¹H NMR, ¹³C NMR, and mass spectrometry, supplemented by elemental analysis to confirm their molecular composition. In addition to the experimental evaluation, the drug-likeness properties of the synthesized compounds were investigated through computational approaches. Molecular docking studies were performed to predict the binding affinities of the Schiff bases with two bacterial protein targets, specifically those with PDB IDs 3UDI and 4CJN. These proteins were chosen for their relevance in bacterial virulence and resistance mechanisms. The docking studies provided insights into the potential interactions between the Schiff bases and the active sites of the target proteins, highlighting key residues involved in binding and suggesting a possible mechanism of action. To further corroborate the docking results and assess the stability of the ligand-protein complexes, molecular dynamics (MD) simulations were conducted over a 100-nanosecond timescale. The MD simulations allowed us to monitor the behavior of the Schiff base-protein complexes in a dynamic environment, providing a more realistic representation of their interactions in vivo. The outcomes of the simulations indicated that the complexes remained stable throughout the simulation period, with minimal fluctuations in the root mean square deviation (RMSD) values, thereby confirming the robustness of the binding interactions. Among the synthesized compounds, CF5 and CF15 emerged as particularly promising candidates, exhibiting not only potent antimicrobial activity but also favorable binding characteristics in the docking studies. The combination of robust experimental data and computational analyses provides a strong foundation for further exploration of these compounds in drug development pipelines.