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  • Title: Synthesis and biological activities of 2-amino-1-arylidenamino imidazoles as orally active anticancer agents.
    Author: Li WT, Hwang DR, Song JS, Chen CP, Chuu JJ, Hu CB, Lin HL, Huang CL, Huang CY, Tseng HY, Lin CC, Chen TW, Lin CH, Wang HS, Shen CC, Chang CM, Chao YS, Chen CT.
    Journal: J Med Chem; 2010 Mar 25; 53(6):2409-17. PubMed ID: 20170097.
    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.
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