In this research, some novel Schiff base derivatives 10-18 were synthesized for the first time, character-ized, and tested for their anticancer activities. Spectroscopic characterization of the synthesized molecules 1-18 was carried out by using elemental analysis (C, H, N, S), FT-IR, HRMS, H-1 -and( 13 )C-NMR and DEPT -135 spectroscopic techniques. The antiproliferative activity studies of all newly synthesized compounds were tested against different human cancer cell lines, including colon and liver, using an MTT assay for 48 h. Under specified experimental conditions, three molecules (13-15) demonstrated higher cytotoxic ac-tivity than other molecules (1-12, 16-18) toward human epithelial colon colorectal cancer cell line (DLD-1) with IC(50 )values of 67.88, 56.53, and 48.70 mu M, respectively. Besides, two different molecules (8 and 17) were found to have more toxic effects than molecules (1-7, 9-16, 18) against human liver epithelial hepatocellular carcinoma cell line (HepG2) with IC50 values of 65.72 and 54.84 mu M, respectively. The se-lectivity of these compounds, which show high activity, was also tested on a healthy human cell line (Wl-38). Compounds (1-18) were docked against target proteins (PDB ID: 5ETY and 6V9C) representing DLD-1 and HepG2 cell lines. (C) 2022 Elsevier B.V. All rights reserved.