کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10584267 | 981327 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
New insights into molecular recognition of 1,1-bisphosphonic acids by farnesyl diphosphate synthase
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: New insights into molecular recognition of 1,1-bisphosphonic acids by farnesyl diphosphate synthase New insights into molecular recognition of 1,1-bisphosphonic acids by farnesyl diphosphate synthase](/preview/png/10584267.png)
چکیده انگلیسی
As part of our project pointed at the search of new antiparasitic agents against American trypanosomiasis (Chagas disease) and toxoplasmosis a series of 2-alkylaminoethyl-1-hydroxy-1,1-bisphosphonic acids has been designed, synthesized and biologically evaluated against the etiologic agents of these parasitic diseases, Trypanosoma cruzi and Toxoplasma gondii, respectively, and also towards their target enzymes, T. cruzi and T. gondii farnesyl pyrophosphate synthase (FPPS), respectively. Surprisingly, while most pharmacologically active bisphosphonates have a hydroxyl group at the C-1 position, the additional presence of an amino group at C-3 resulted in decreased activity towards either T. cruzi cells or TcFPPS. Density functional theory calculations justify this unexpected behavior. Although these compounds were devoid of activity against T. cruzi cells and TcFPPS, they were efficient growth inhibitors of tachyzoites of T. gondii. This activity was associated with a potent inhibition of the enzymatic activity of TgFPPS. Compound 28 arises as a main example of this family of compounds exhibiting an ED50 value of 4.7 μM against tachyzoites of T. gondii and an IC50 of 0.051 μM against TgFPPS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 1, 1 January 2014, Pages 398-405
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 1, 1 January 2014, Pages 398-405
نویسندگان
Mariana Ferrer-Casal, Catherine Li, Melina Galizzi, Carlos A. Stortz, Sergio H. Szajnman, Roberto Docampo, Silvia N.J. Moreno, Juan B. Rodriguez,