A series of novel hydrazinecarbothioamide, 1,2,4-triazole-3-thione, 4-thiazolidinone and 1,3,4-oxadiazole derivatives were synthesized and evaluated for their cytotoxic activity against A549 lung adenocarcinoma cells and L929 normal mouse fibroblast cell line. The structural elucidation of the compounds was per-formed and verified by IR spectroscopy, 1H-NMR, 13C-NMR, mass and elemental analysis. Compound 3a, 3b, 3c, 3d, 3e, 3g and 3i displayed the best anticancer activity against A-549 cell line. The anticancer activities of 3a, 3c, 3d, 3e, 3g and 3i were determined as better than the positive control Cisplatin. In addition to the in vitro analysis, molecular docking studies were employed to explore the possible binding interactions of the title compounds with B-DNA (PDB ID: 1BNA) dodecamer d(CGCGAATTCGCG)2. Structure-activity relationships, as well as virtual ADME studies, were carried out and a relationship be-tween biological, electronic, and physicochemical qualifications of the target compounds was determined. Consequently, these derivatives present a leading structure for future drug development due to their straightforward synthesis and relevant bioactivity. (C) 2022 Elsevier B.V. All rights reserved.