New molecules candidates with semicarbazide scaffold – anticancer potential in view of research on their physicochemical properties and antioxidant activity

Developing semicarbazide-based compounds as potential therapeutic agents is a promising direction in medicinal chemistry, particularly in the context of anticancer drug design. This study reports the synthesis and comprehensive physicochemical characterization of a series of novel semicarbazide derivatives ( AW8, AW12, AW19, AW23, AW33, AW38 ). Their molecular structures and tautomeric forms in the crystalline state were elucidated using single-crystal X-ray diffraction and supported by detailed FTIR spectroscopic analysis. The compounds exhibited distinct hydrogen-bonding patterns, conformational preferences depending on their substituent type and characteristic intermolecular interactions governing their crystal packing as confirmed by Hirshfeld surface analysis. Incorporation into DPPC-based model lipid membranes was evaluated using ATR-FTIR and Langmuir monolayer techniques. AW8 and AW12 showed the strongest interactions with the phospholipid model membrane, inducing significant spectral alterations and surface pressure changes, indicative of membrane affinity modulated by chlorine substitution. ADMET predictions revealed favourable pharmacokinetic properties, including blood-brain barrier permeability for selected derivatives and inhibition of P-glycoprotein, a key mediator of multidrug resistance. Antioxidant potential was assessed by DPPH and ABTS assays, demonstrating moderate free radical scavenging activity. These findings suggest that the studied semicarbazides exhibit promising bioactivity and physicochemical features supporting further biological evaluation as membrane-active drug candidates.