title: Synthesis and biological evaluation of N-heterocyclic indolyl glyoxylamides as orally active anticancer agents.
abstract: A series of N-heterocyclic indolyl glyoxylamides were synthesized and evaluated for in vitro and in vivo anticancer activities. They exhibited a broad spectrum of anticancer activity not only in murine leukemic cancer cells but also in human gastric, breast, and uterus cancer cells as well as their multidrug resistant sublines with a wide range of IC(50) values. They also induced apoptosis and caused DNA fragmentation in human gastric cancer cells. Among the compounds studied, 7 showed the most potent activity of growth inhibition (IC(50) = 17-1711 nM) in several human cancer cells. Given orally, compounds 7 and 13 dose-dependently prolonged the survival of animals inoculated with P388 leukemic cancer cells. N-Heterocyclic indolyl glyoxylamides may be useful as orally active chemotherapeutic agents against cancer and refractory cancerous diseases of multidrug resistance phenotype.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 9F, 161, Sec. 6, Min-Chiuan East Road, Nei-Hu, Taipei 114, Taiwan, ROC.
authors.forename: Wen-Tai
authors.initials: WT
authors.lastname: Li
authors.forename: Der-Ren
authors.initials: DR
authors.lastname: Hwang
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Shen
authors.forename: Chen-Long
authors.initials: CL
authors.lastname: Huang
authors.forename: Tung-Wei
authors.initials: TW
authors.lastname: Chen
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Yee-Ling
authors.initials: YL
authors.lastname: Chang
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Chang
authors.forename: Yue-Kan
authors.initials: YK
authors.lastname: Lo
authors.forename: Huan-Yi
authors.initials: HY
authors.lastname: Tseng
authors.forename: Chu-Chung
authors.initials: CC
authors.lastname: Lin
authors.forename: Jeng-Shin
authors.initials: JS
authors.lastname: Song
authors.forename: Hua-Chien
authors.initials: HC
authors.lastname: Chen
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Se-Hui
authors.initials: SH
authors.lastname: Wu
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006038:Glyoxylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007941:Leukemia P388 / Q000401:mortality; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006038:Glyoxylates; D007211:Indoles; C474151:N1-(3-methyl-5-isothiazolyl)-2-(1-(4-cyanobenzyl)-1H-3-indolyl)-2-oxoacetamide; C474150:N1-(3-methyl-5-isothiazolyl)-2-1-((3-methyl-5-isoxazolyl)methyl)-1H-3-indolyl-2-oxoacetamide; D013844:Thiazoles