Objectives: To synthesize Schiff bases i.e 4-((2-hydroxybenzylidene)-amino–N-(5-methyl-1,2-oxozol-3- yl)benzene sulphonamide (L1), 4-((2-hydroxy benzylidene)-amino-N-(thiazol-yl)benzene sulphonamide (L2), 4-((2-hydroxybenzylidene)amino-N-(pyridin-2-yl)benzene sulphonamide by theaction of 2-hydroxybenzaldehyde with sulfathiazole/ sulfamethoxazole/ sulfapyridine in ethanolic media. Methods: The Schiff bases obtained were characterized by analytical data, IR, UV, 1H- NMR, 13C-NMR, Mass spectrum and monitored for cytotoxic activity against human breast cancer cell [MDA MB -231] line. Findings: The Schiff bases behaves as a bidentate ligand with oxygen and nitrogen as chelating positions and coordinates via phenolic oxygen and azomethine nitrogen. The composition of the ligands has been established by elemental analysis. Structural features and bonding mode of the Schiff bases have been proposed by spectral methods. The evaluated synthesized ligand shows excellent cytotoxic activity towards breast cancer cell line. Novelty: The evaluated highly biologically active L1 and L3 shows desirable cytotoxic activity towards [MDA MB -231] breast cancer cell line. The better IC50 value of the Schiff base ligands upgrades as chemotherapeutic agents which leads to drug formulation and induces DNA binding studies. Keywords: 4-amino-N-(1; 3-thiazol-2-yl)benzenesulfonamide; 4-amino-N-(5-methyl-1; 2-oxazol-3-yl)-benzenesulfonamide; 4-amino-N-(pyridin-2-yl)benzenesulphonamide; 2-hydroxy benzaldehyde; cytotoxicity