title: Discovery and structure-activity relationships of (2-(arylthio)benzylideneamino)guanidines as a novel series of potent apoptosis inducers.
abstract: 1-(2-(2,5-Dimethoxyphenylthio)benzylidene)semicarbazide (2a) was discovered as a potent apoptosis inducer through our cell based HTS assay. SAR study led to the discovery of a more aqueous soluble analog (2-(2,5-dimethoxyphenylthio)-6-methoxybenzylideneamino)guanidine (5e) with EC(50) value of 60 nM in the caspase activation assay and GI(50) value of 62 nM in the growth inhibition assay in T47D cells. Compound 5e was found to be an inhibitor of tubulin polymerization and efficacious in a MX-1 breast tumor model.
authors.affiliation: EpiCept Corporation, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Candace
authors.initials: C
authors.lastname: Crogan-Grundy
authors.forename: Chris
authors.initials: C
authors.lastname: May
authors.forename: John
authors.initials: J
authors.lastname: Drewe
authors.forename: Ben
authors.initials: B
authors.lastname: Tseng
authors.forename: Sui Xiong
authors.initials: SX
authors.lastname: Cai
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D012663:Semicarbazides / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C541073:(2-(2,5-dimethoxyphenylthio)-6-methoxybenzylideneamino)guanidine; C541072:1-(2-(2,5-dimethoxyphenylthio)benzylidene)semicarbazide; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D006146:Guanidines; D012663:Semicarbazides; D050257:Tubulin Modulators