The objectives of this work is comparing three different kinds of sulfonamide compounds by evaluating structure modification through their examination towards more important properties such as: (a) Surface properties of the synthesized sulfonamide compounds were studied through surface parameters ?cmc,(cmc), A(min) and ?(max). Most of these tested compounds have remarkable surface activity. (b) The target compounds were tested to determine structure-biological activity relationship against different types of pathogenic bacterial species. The amine acid salts of bis (2-aminophenyl) biphenyl-4,4''-disulfonamide (Series B) were the powerfully effective series. Only carboxylic acid salts of bis (2-aminophenyl)biphenyl-4,4''- disulfonamide (Series B) were powerfully effective series against selected pathogenic fungal species. (c) Selected compounds were screened for cytotoxicity against selected human tumor cell lines – MCF7, HEPG2, and HCT116. Most of tested compounds have potent cytotoxic activity against liver carcinoma and colon carcinoma, meanwhile, exhibit moderate activity against breast carcinoma.