title: Synthesis and biological evaluation of cyanoguanidine derivatives of loratadine.
abstract: Cyanoguanidine derivatives of loratadine (3a-i) were synthesized and screened for antitumor and anti-inflammatory activity. The most promising compound 3c (R=n-C(8)H(17)) possessed at least twofold higher in vitro cytotoxicity than 5-fluorouracil against mammary (MCF-7 and MDA-MB 231) as well as colon (HT-29) carcinoma cells. The mode of action, however, is so far unclear. The participation of the COX-1/2 enzymes on the cytotoxicity, however, is very unlikely. Nevertheless all compounds showed stronger in vivo anti-inflammatory activity than ibuprofen in the xylene-induced ear swelling assay in mice.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Tongjia Xiang 24, 210009 Nanjing, PR China.
authors.forename: Wukun
authors.initials: W
authors.lastname: Liu
authors.forename: Jinpei
authors.initials: J
authors.lastname: Zhou
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Huibin
authors.initials: H
authors.lastname: Zhang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhu
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Cheng
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004427:Ear Diseases / Q000139:chemically induced / Q000188:drug therapy*; D006146:Guanidines / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D017336:Loratadine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014992:Xylenes
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D006146:Guanidines; D014992:Xylenes; D017336:Loratadine; C004711:dicyandiamido