ABSTRACT
Two series of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB). Extensive structure-activity relationships (SAR) were studied within these series. Several compounds were found to be novel and selective COX-2 inhibitors. Among them, the most potent and selective was 4-(3-carboxy-4-hydroxy-benzylideneamino)benzenesulfonamide (20, LA2135), (IC(50)'s for COX-1: 85.13 microM; COX-2: 0.74 microM; SI: 114.5), being more active COX-2 selective than celecoxib.
Subject(s)
Benzylidene Compounds/chemical synthesis , Benzylidene Compounds/pharmacology , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/pharmacology , Imines/chemistry , Sulfonamides/chemical synthesis , Sulfonamides/pharmacology , Amination , Benzylidene Compounds/chemistry , Blood Platelets/drug effects , Blood Platelets/enzymology , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/chemistry , Humans , Methylation , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemistry , BenzenesulfonamidesABSTRACT
A series of phenylazobenzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB) and an enzymatic assay using purified ovine enzymes. Extensive structure-activity relationships (SAR) were studied within this series, and several of selective COX-2 inhibitors have been identified. Among them, compound 8, 4-(4-amino-2-methylsulfanyl-phenylazo)benzenesulfonamide, showed a potent inhibitory activity to the cyclooxygenase enzymes (IC(50)'s for COX-1: 23.28 microM; COX-2: 2.04 microM), being active but less COX-2 selective than celecoxib.
Subject(s)
Azo Compounds/chemical synthesis , Azo Compounds/pharmacology , Blood Cells/drug effects , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/pharmacology , Sulfonamides/chemical synthesis , Sulfonamides/pharmacology , Azo Compounds/chemistry , Blood Cells/enzymology , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/chemistry , Humans , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemistryABSTRACT
A new series of trans-stilbene benzenesulfonamide derivatives were designed and synthesized as potential antitumor agents. These new compounds were evaluated in the National Cancer Institute's 60 human tumor cell line in vitro screen. Compounds 9-13 were cytotoxic against several cell lines. Notably, two compounds, 9 and 12, demonstrated selective cytotoxic activity against BT-549 breast cancer (GI(50)=0.205 microM) and HT-29 colon cancer (GI(50)=0.554 microM), respectively.
