title: From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation.
abstract: Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure-function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC(50)s around 100 nM-200 nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC(50)s around 100 nM-500 nM. Intraperitoneal injection with a dosage of 5  mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound.
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.
authors: Bo
authors: B
authors: Zhong
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.
authors: Xiaohan
authors: X
authors: Cai
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.
authors: Snigdha
authors: S
authors: Chennamaneni
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.
authors: Xin
authors: X
authors: Yi
authors: Division of Hematology and Oncology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors: Lili
authors: L
authors: Liu
authors: Division of General Medical Sciences-Oncology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors: John J
authors: JJ
authors: Pink
authors: Division of Hematology and Oncology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors: Afshin
authors: A
authors: Dowlati
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.
authors: Yan
authors: Y
authors: Xu
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.|Center for Gene Regulation in Health and Disease, College of Sciences & Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.
authors: Aimin
authors: A
authors: Zhou
authors: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.|Center for Gene Regulation in Health and Disease, College of Sciences & Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH, 44115, USA.
authors: Bin
authors: B
authors: Su
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D052117:Benzodioxoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D015195:Drug Design; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D051381:Rats; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; C574650:benzo(1,3)dioxole-5-carboxylic acid (3-(2,5-dimethylbenzyloxy)-4-(methanesulfonylmethylamino)phenyl)amide; D051546:Cyclooxygenase 2; C012655:nimesulide