کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1398934 1501139 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Bisphosphonate prodrugs: Synthesis and biological evaluation in HuH7 hepatocarcinoma cells
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Bisphosphonate prodrugs: Synthesis and biological evaluation in HuH7 hepatocarcinoma cells
چکیده انگلیسی


• New bisphosphonates prodrugs have been synthesized.
• The parent bisphosphonate has been released via phosphodiesterase hydrolysis.
• Diphenyl bisphosphonate 2a showed the best antitumour activity in vitro.

We investigated the biological effects of new synthesized bisphosphonates (BPs) on HuH7 hepatocarcinoma cells. BPs containing p-bromophenyl (R1 = p-Br, Ph, 2) in their side chain were the more potent to inhibit HuH7 cell viability. In addition, phenyl diesterified analogues (R2 = R3 = Ph, 2a) were more potent than methyl (R2 = R3 = Me, 2b) or non-esterified BPs (2) inducing more necrosis suggesting that they better entered into cells. Phosphodiesterase inhibitor (IBMX) reversed the effect of the esterified BPs and not that of non-esterified ones suggesting role of cell phosphodiesterases to release active BPs. BP analogues inhibited HuH7 cell migration but esterified ones had no effect on invasion due to the hiding of phosphonic groups. All together, these results indicated the therapeutic interest of these new BP prodrugs.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 77, 22 April 2014, Pages 56–64
نویسندگان
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