کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10586704 | 981395 | 2011 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: 1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4 1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4](/preview/png/10586704.png)
چکیده انگلیسی
A series of 1,1-diarylalkene derivatives were prepared to optimize the properties of CC-5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase 4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the aromatic rings, a significant improvement in PDE4 inhibition was achieved. Compound 28 was identified as a dual inhibitor with potent PDE4 (IC50 = 54 nM) and antitubulin activity (HCT-116 IC50 = 34 nM and tubulin polymerization IC50 â¼1 μM). While the nitrile group at the alkene terminus was generally required for potent antiproliferative activity, its replacement was tolerated if there was a hydroxyl or amino group on one of the aryl rings. Conveniently, this group could also serve as a handle for amino acid derivatization to improve the compounds' solubility. The glycinamide analog 45 showed significant efficacy in the HCT-116 xenograft model, with 64% inhibition of tumor growth upon dosing at 20 mg/kg qd.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 21, 1 November 2011, Pages 6356-6374
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 21, 1 November 2011, Pages 6356-6374
نویسندگان
Alexander L. Ruchelman, Hon-Wah Man, Roger Chen, Wei Liu, Ling Lu, Dorota Cedzik, Ling Zhang, Jim Leisten, Alice Collette, Rama Krishna Narla, Heather K. Raymon, George W. Muller,