کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10584345 | 981329 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synthesis and evaluation of Strychnos alkaloids as MDR reversal agents for cancer cell eradication
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Synthesis and evaluation of Strychnos alkaloids as MDR reversal agents for cancer cell eradication Synthesis and evaluation of Strychnos alkaloids as MDR reversal agents for cancer cell eradication](/preview/png/10584345.png)
چکیده انگلیسی
Natural products represent the fourth generation of multidrug resistance (MDR) reversal agents that resensitize MDR cancer cells overexpressing P-glycoprotein (Pgp) to cytotoxic agents. We have developed an effective synthetic route to prepare various Strychnos alkaloids and their derivatives. Molecular modeling of these alkaloids docked to a homology model of Pgp was employed to optimize ligand-protein interactions and design analogues with increased affinity to Pgp. Moreover, the compounds were evaluated for their (1) binding affinity to Pgp by fluorescence quenching, and (2) MDR reversal activity using a panel of in vitro and cell-based assays and compared to verapamil, a known inhibitor of Pgp activity. Compound 7 revealed the highest affinity to Pgp of all Strychnos congeners (Kd = 4.4 μM), the strongest inhibition of Pgp ATPase activity, and the strongest MDR reversal effect in two Pgp-expressing cell lines. Altogether, our findings suggest the clinical potential of these synthesized compounds as viable Pgp modulators justifies further investigation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 3, 1 February 2014, Pages 1148-1155
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 3, 1 February 2014, Pages 1148-1155
نویسندگان
Surendrachary Munagala, Gopal Sirasani, Praveen Kokkonda, Manali Phadke, Natalia Krynetskaia, Peihua Lu, Frances J. Sharom, Sidhartha Chaudhury, Mohamed Diwan M. Abdulhameed, Gregory Tawa, Anders Wallqvist, Rogelio Martinez, Wayne Childers,