کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10587832 | 981440 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synthesis and characterization of tritylthioethanamine derivatives with potent KSP inhibitory activity
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Assembly of a bipolar mitotic spindle requires the action of class 5 kinesins, and inhibition or depletion of this motor results in mitotic arrest and apoptosis. S-Trityl-l-cysteine is an allosteric inhibitor of vertebrate Kinesin Spindle Protein (KSP) that has generated considerable interest due to its anti-cancer properties, however, poor pharmacological properties have limited the use of this compound. We have modified the triphenylmethyl and cysteine groups, guided by biochemical and cell-based assays, to yield new cysteinol and cysteamine derivatives with increased inhibitory activity, greater efficacy in model systems, and significantly enhanced potency against the NCI60 tumor panel. These results reveal a promising new class of conformationally-flexible small molecules as allosteric KSP inhibitors for use as research tools, with activities that provide impetus for further development as anti-tumor agents.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 18, 15 September 2011, Pages 5446-5453
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 18, 15 September 2011, Pages 5446-5453
نویسندگان
Delany Rodriguez, Chinnasamy Ramesh, Lauren H. Henson, Lori Wilmeth, Bj K. Bryant, Samuel Kadavakollu, Rebecca Hirsch, Johnelle Montoya, Porsha R. Howell, Jon M. George, David Alexander, Dennis L. Johnson, Jeffrey B. Arterburn, Charles B. Shuster,