Investigation of the anticancer potential of newly synthesized N4-substituted thiosemicarbazones: In silico and in vitro biological approaches

Four thiosemicarbazones by using tolualdehyde and cuminaldehyde having the formula, R²−(S)C−HN−NHC−R¹[R¹ = CH₃ & R² = C₄H₉N (TAP), R² = C₄H₉NO & R¹ = CH₃ & (TAM), R² = C₄H₉N & R¹ = (CH₃)₂CH (CMP), R² = C₄H₉NO & R¹ = (CH₃)₂CH (CMM)] have been synthesized. The compound interactions were assessed using their UV−visible, infrared, NMR, and HRMS spectra. Single−crystal X−ray diffraction was employed to know the molecular structure of CMP and TAP. The compounds were assessed for their interactions with Calf−Thymus (CT)−DNA using spectroscopic titrations using both emission and absorption spectra. As per the research findings on DNA binding, the compounds interactively interacted with DNA, as indicated by the hypochromic and slight red shift. TAP exhibited a high binding constant (5.16 × 10⁵), suggesting a stronger binding to CT−DNA compared to other compounds. The fluorescence titration spectra of BSA binding experiments exhibited a noteworthy hypochromic shift and red shift, displaying a strong interaction of chemicals with BSA. EGFR protein docking examination demonstrated the potential of compounds to treat the targets. TAP displayed the highest binding score (–6.4230 Kcal/mol) to EGFR with the four compounds. To compute density functional theory (DFT), B3LYP/6−311 G (d, p) level theories have been implemented. Generated compounds' computational analyses reveal the structural stability of compound TAP than the rest synthesized ligands. SwissADME investigations indicate that the LogP values for each compound are less than five indicating that they have the right lipophilicity characteristics. All newly synthesized compounds follow Lipinski's rule of drug lines. A good result for this characteristic is indicated by the low degree of synthetic accessibility, which falls between two and three. Each of the compounds (TAP−CMM) can develop into a viable oral medicine. Each compound (TAP−CMM) was tested for its anticancer potential using MCF−7, MCF−10A, A549, and human HepG−2 liver. TAP demonstrated favorable efficacy in HepG−2 liver cancer cells, exhibiting IC₅₀ values of 23.1 μM.