Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase inhibitor resistance in breast cancer cells.
A series of COX-2 selective inhibitor nimesulide derivatives were synthesized. Their anti-cell proliferation activities were evaluated with a long-term estrogen deprived MCF-7aro (LTEDaro) breast cancer cell line, which is the biological model of aromatase inhibitor resistance for hormone-dependent breast cancer. Compared to nimesulide which inhibited LTEDaro cell proliferation with an IC(50) at 170.30 microM, several new compounds showed IC(50) close to 1.0 microM.
Su
Bin
B
Division of Tumor Cell Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Chen
Shiuan
S
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; C012655:nimesulide