Design, Novel Synthesis and Biological Evaluation of Chalcone Derivatives Based on Pyrazole Carbaldehyde Moiety

Abstract Chalcones are recognized as privileged scaffolds that exhibit a wide spectrum of biological activities, while pyrazole derivatives are well known for their significant pharmacological potential. In the present study, a novel series of chalcone derivatives bearing a 3-phenyl-1H-pyrazole-4-carbaldehyde moiety was designed, synthesized, and subjected to biological evaluation. The target compounds were synthesized via base-catalyzed Claisen-Schmidt condensation between substituted heterocyclic acetophenones and 1,3-diphenyl pyrazole-4-carbaldehydes, affording the desired chalcones in good yields. The structures of the synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analyses. Biological evaluation revealed that several derivatives showed favorable antimicrobial activity against certain Gram-positive and Gram-negative bacterial strains, as well as against fungal species, when compared with standard drugs. Preliminary structure–activity relationship (SAR) analysis indicated that the nature and position of the substituents on the aromatic ring significantly influenced biological activity, with electron-withdrawing groups showing enhanced potency. These results suggest that chalcones bearing a pyrazole-carbaldehyde moiety represent a promising framework for the development of new biologically active agents and warrant further optimization and mechanistic studies.