کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1356997 981184 2006 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450
چکیده انگلیسی

Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency of the P-glycoprotein (P-gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6 carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp inhibitors. The maximal inhibition was obtained when using an ethyl or propyl spacer. Several compounds were more potent than verapamil and intrinsically less cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. In this context, 22a might be a suitable candidate for further drug development.

Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators were performed to assess their potency to inhibit P-glycoprotein and CYP450.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 23, 1 December 2006, Pages 7972–7987
نویسندگان
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