Photophysical and biological studies on structurally modified chlorophenyl-substituted pyrazolone derivatives

In this study, chlorophenyl-substituted pyrazolone derivatives (5a–5c) were synthesized via the Baylis-Hillman acetate reaction. Comprehensive physicochemical characterization was conducted using ¹H-NMR, FT-IR, and mass spectroscopy. Density Functional Theory (DFT) calculations at the B3LYP/6-31(G) level was employed to optimize molecular geometries and investigate electronic properties, revealing predominantly planar structures, with notable deviations in the pyrazole group. The HOMO and LUMO analyses showed π-delocalization across the entire molecule, with charge-transfer transitions dominating the excited states. Global Chemical Reactivity Descriptors (GCRD), including chemical potential, hardness, and electrophilicity index, were used to assess molecular stability and reactivity, indicating the molecules’ resistance to electron cloud deformation. Biological evaluations revealed exceptional antimicrobial and antifungal activities of the derivatives, with compound 5a demonstrating the highest efficacy against S. aureus, E. coli, A. niger and C. albicans. Furthermore, antiproliferative studies against HepG2 liver carcinoma cells showed that compound 5a exhibited superior anticancer activity (IC50 = 6 μg/mL), attributed to its structural features, such as chlorophenyl groups and a piperidin-4-one moiety. These moieties enhance the compound’s lipophilicity, facilitating cell membrane penetration and ROS generation, which contribute to apoptosis and inhibition of cancer cell growth. The findings suggest that chlorophenyl-pyrazolone derivatives, particularly 5a, hold promise as potent candidates for antimicrobial and anticancer therapies, paving the way for further pharmaceutical development.