title: Synthesis and biological activities of 2-amino-1-arylidenamino imidazoles as orally active anticancer agents.
abstract: 2-Amino-1-arylidenaminoimidazoles, a novel class of orally (po) active microtubule-destabilizing anticancer agents, were synthesized. The compounds were designed from a hit compound identified in a drug discovery platform by using cancer cell-based high throughput screening assay. Selective synthesized compounds exerted cell cytotoxicity against human cancer cells. The underlying mechanisms for the anticancer activity were demonstrated as interacting with the tubulins and inhibiting microtubule assembly, leading to proliferation inhibition and apoptosis induction in the human tumor cells. Furthermore, two compounds showed in vivo anticancer activities in both po and intravenously (iv) administered routes and prolonged the life spans of murine leukemic P388 cells-inoculated mice. These new po active antimitotic anticancer agents are to be further examined in preclinical studies and developed for clinical uses.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 35053, Taiwan, ROC.
authors.forename: Wen-Tai
authors.initials: WT
authors.lastname: Li
authors.forename: Der-Ren
authors.initials: DR
authors.lastname: Hwang
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Song
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Chuu
authors.forename: Chih-Bo
authors.initials: CB
authors.lastname: Hu
authors.forename: Heng-Liang
authors.initials: HL
authors.lastname: Lin
authors.forename: Chen-Lung
authors.initials: CL
authors.lastname: Huang
authors.forename: Chiung-Yi
authors.initials: CY
authors.lastname: Huang
authors.forename: Huan-Yi
authors.initials: HY
authors.lastname: Tseng
authors.forename: Chu-Chung
authors.initials: CC
authors.lastname: Lin
authors.forename: Tung-Wei
authors.initials: TW
authors.lastname: Chen
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Hsin-Sheng
authors.initials: HS
authors.lastname: Wang
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Shen
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Chang
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007941:Leukemia P388 / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D014404:Tubulin