Synthesis and characterization of N4-substituted thiosemicarbazones: DNA/BSA binding, molecular docking, anticancer activity, ADME study and computational investigations.

• N4 -substituted thiosemicarbazones with morpholine and pyrrolidine moiety were synthesized using different aldehydes, characterized. • DNA/BSA binding studies were performed with absorption and emission spectroscopy and the mode of binding, binding constant values are discovered. • The binding capacity of the ligands with BSA were also investigated through molecular docking studies. • Theoretical calculations are accomplished using DFT method to get the electronic structural properties of ligands TL1-TL4. • The low degree of synthetic accessibility ranges from 2–3, indicating a quality result for this characteristic in Swiss-ADME studies. • Anticancer activity were investigated on human HepG-2-liver, EAhy-926-endothelial carcinoma cancer and african green monkey normal vero cells. A series of thiosemicarbazones with the general formula, R − CH N − NH − C(S) − R 1 [R = C 6 H 5 F & R 1 = C 4 H 9 NO (TL1), R = C 8 H 10 O 2 & R 1 = C 4 H 9 NO (TL2), R = C 6 H 5 F & R 1 = C 4 H 9 N (TL3), R = C 6 H 5 Br & R 1 = C 4 H 9 N (TL4)] were synthesized. The UV–Visible, Infra-red, NMR and HRMS spectra were used to confirm compounds. The single-crystal X-ray diffraction (XRD) technique was used to determine the molecular composition of TL3 and TL4. Absorption/emission spectroscopic titrations were subjected to evaluate the compounds' interactions with Calf-Thymus (CT) DNA. According to DNA binding research findings, the compounds were bound to DNA in an interactive manner, as evidenced by the hypochromic and slight red shift. The compound TL3 possesses a high binding constant (5.17 × 106 M−1), which indicates that it bound CT-DNA more firmly than other compounds. The red shift and strong hypochromic shift observed in the fluorescence titration spectrum of BSA binding studies described a strong interaction of compounds with BSA. The compound TL3 exhibits a redshift of 3 nm and 92% quenching. The BSA protein docking studies of the compounds revealed their ability to act as medicines for the targets. Amongst the four compounds, TL3 shows high binding energy towards BSA (̶ 6.33 Kcal/mol) protein. B3LYP/ 6–311 G (d, p) level theories were used to compute density functional theory (DFT). Computational evaluations of the generated compounds show that the compound TL2 has significantly higher structural stability than other compounds. According to SwissADME studies, the LogP values for all compounds were less than 5, indicating appropriate lipophilicity characteristics. The low degree of synthetic accessibility ranges from 2–3, indicating a quality result for this characteristic. In other words, all the compounds TL1-TL4 have the potential to evolve into good oral drug candidates. Anticancer activity of four compounds (TL1-TL4) was investigated on human HepG-2-liver, EAhy-926-endothelial carcinoma cancer and African green monkey normal Vero cells. The compound TL3 showed good activity in liver and endothelial carcinoma cancer cells with IC 50 values of 37.5 and 30.1 µM, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]