Synthesis of substituted imidazo[2,1-b]-1,3,4-thiadiazoles 2a,b-6, substituted 1,3,4-thiadiazolo[3,2-a]pyrimidines 7- 9 and 1,3-disubstituted thioureas 10a-e was reported. Structures of all synthesized compounds were elucidated using IR, NMR and mass spectroscopy. All the prepared derivatives were evaluated for their cytotoxic activity against tumor cell line A549 (Non-Small Cell Lung Cancer Cell Line) using Sulfo-Rodamine B (SRB) standard method. Most of the tested compounds exhibited potent cytotoxicity especially compounds 4, 5, 8 and 10b-d (IC50 2.58-6.47 μM). In order to find a molecular target for newly synthesized compounds, docking study was performed to explore the possible binding mode of these compounds with the binding site of fibroblast stromelysin-1 enzyme, which is involved in several pathological conditions including cancer.