title: Synthesis and structure-activity relationships of N-aryl(indol-3-yl)glyoxamides as antitumor agents.
abstract: The synthesis and study of the structure-activity relationships of cytotoxic compounds based on N-pyridinyl or N-aryl-2-(1-benzylindol-3-yl)glyoxamide skeleton, represented by the lead structures D-24241 and D-24851, are described. The presence of N-(pyridin-4-yl) moiety was crucial for activity and 2-[1-(4-chloro-3-nitrobenzyl)-1H-indol-3-yl]-2-oxo-N-(pyridin-4-yl)acetamide (55), the most potent derivative, showed IC(50)=39 nM, 51 nM and 11 nM against HeLa/KB (human cervix carcinoma), L1210 (murine leukemia) and SKOV3 (human ovarian carcinoma) cell lines proliferation assay, respectively, as active as the lead compounds.
authors.affiliation: Nantes Université, Nantes Atlantique Universités, Département de Pharmacochimie, IICiMed UPRES EA 1155, Faculté de Pharmacie, 1 rue Gaston Veil 44035 Nantes, France. pascal.marchand@univ-nantes.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Marchand
authors.forename: Maud
authors.initials: M
authors.lastname: Antoine
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Baut
authors.forename: Michael
authors.initials: M
authors.lastname: Czech
authors.forename: Silke
authors.initials: S
authors.lastname: Baasner
authors.forename: Eckhard
authors.initials: E
authors.lastname: Günther
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013453:Sulfonylurea Compounds; C032160:glyoxamide