Synthesis, crystal structure, hirshfeld surface analysis, and inhibition of urease and carbonic anhydrase by azomethine compounds

Azomethines possess tremendous potential as drugs, pharmaceuticals, agrochemicals, and material applications. Herein, molecular iodine catalyzed synthesis of new Schiff bases (SB-1 to SB-5) derived from 4-Phenoxyaniline and 4-Chloroaniline with substituted benzaldehydes is reported. FT-IR and 1H- and 13C NMR spectroscopic methods authenticated the synthesized Schiff bases. Moreover, the crystal structures of SB-3 and SB-5 were determined by single-crystal X-ray diffraction (SC-XRD) method. In both structures, the terminal phenyl rings were twisted related to the central phenyl ring but the twist was larger for SB-5 due to large dihedral angles between the rings. C-H & ctdot;O interactions were observed only in SB-3, whereas C-H & ctdot;pi interactions were found in both compounds. The intermolecular interactions were responsible for stabilizing the supramolecular assembly, evidenced by Hirshfeld surface analysis. The enrichment ratios explored the pair of atoms with the highest tendency to form crystal-packing interactions. Evaluation of SB-1 to SB-5 against urease and carbonic anhydrase showed that SB-2 behaves as a dual inhibitor of urease (IC50 = 2.7 +/- 0.24 mu M) and carbonic anhydrase (IC50 = 1.28 +/- 0.46 mu M). SB-3 and standard drug were subjected to extensive molecular dynamics (MD) simulations to understand the binding mode of interaction of the compound with the protein.