Synthesis, β-Cyclodextrin Encapsulation, and Biological Screening of Novel Azomethine Derivatives: A Host–Guest Approach to Enhanced Pharmacological Activity

A novel Schiff base, (E)-4-((5-bromo-2-hydroxy-3-methoxybenzylidene) amino)-1,5-dimethyl-2- phenylpyrazolidin-3-one (SB), was synthesized via condensation of 4-aminoantipyrine with 5-bromo-2- hydroxy-3-methoxybenzaldehyde (isovanillin bromide) under acid-catalyzed conditions and subsequently encapsulated within β-cyclodextrin (β-CD) to fabricate a host–guest inclusion complex. The Schiff base was characterized by FT-IR, ¹H NMR, ¹³C NMR and mass spectrometry, confirming the formation of the azomethine (C=N) linkage. Inclusion complex formation between SB and β-CD was confirmed through solid-state characterization employing powder X-ray diffraction (PXRD) , which revealed significant amorphization of the crystalline guest and host lattices—providing unambiguous evidence of genuine molecular encapsulation. The β-CD inclusion complex demonstrated markedly enhanced aqueous solubility and physicochemical stability relative to the free Schiff base SB. The β-CD encapsulated complex exhibited significantly improved biological potency across all assays compared to the uncomplexed Schiff base, attributable to enhanced bioavailability and membrane permeability conferred by β-CD complexation. The presence of the bioactive 4-aminoantipyrine scaffold, bromine substituent, and phenolic hydroxyl group in SB are proposed as key pharmacophoric features contributing to the observed activities. These findings highlight the therapeutic promise of the SB/β-CD system and underscore the utility of cyclodextrin-based encapsulation as a versatile strategy to augment the pharmaceutical performance of Schiff base drug candidates.