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Research in Pharmaceutical Sciences، جلد ۱۸، شماره ۵، صفحات ۵۰۵-۵۱۶
عنوان فارسی
چکیده فارسی مقاله
کلیدواژه‌های فارسی مقاله
عنوان انگلیسی Bioinformatic analysis of highly consumed phytochemicals as P-gp binders to overcome drug-resistance
چکیده انگلیسی مقاله Background and purpose: P-glycoprotein (P-gp) is an adenosine triphosphate (ATP)-dependent membrane efflux pump for protecting cells against xenobiotic compounds. Unfortunately, overexpressed P-gp in neoplastic cells prevents cell entry of numerous chemotherapeutic agents leading to multidrug resistance (MDR). MDR cells may be re-sensitized to chemotherapeutic drugs via P-gp inhibition/modulation. Side effects of synthetic P-gp inhibitors encouraged the development of natural products. Experimental approach: Molecular docking and density functional theory (DFT) calculations were used as fast and accurate computational methods to explore a structure binding relationship of some dietary phytochemicals inside distinctive P-gp binding sites (modulatory/inhibitory). For this purpose, top-scored docked conformations were subjected to per-residue energy decomposition analysis in the B3LYP level of theory with a 6-31g (d, p) basis set by Gaussian98 package. Findings/Results: Consecutive application of computational techniques revealed binding modes/affinities of nutritive phytochemicals within dominant binding sites of P-gp. Blind docking scores for best-ranked compounds were superior to verapamil and rhodamine-123. Pairwise amino acid decomposition of superior docked conformations revealed Tyr303 as an important P-gp binding residue. DFT-based induced polarization analysis revealed major electrostatic fluctuations at the atomistic level and confirmed larger effects for amino acids with energy-favored binding interactions. Conformational analysis exhibited that auraptene and 7,4',7'',4'''-tetra- O -methylamentoflavone might not necessarily interact to P-gp binding sites through minimum energy conformations. Conclusion and implications: Although there are still many hurdles to overcome, obtained results may propose a few nutritive phytochemicals as potential P-gp binding agents. Moreover; top-scored derivatives may have the chance to exhibit tumor chemo-sensitizing effects.
کلیدواژه‌های انگلیسی مقاله Chemosensitizers,Molecular docking,Multidrug resistance,P-gp,Phytochemicals.
نویسندگان مقاله | Narges Rajaei
Students Research Committee, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.


| Ghazaleh Rahgouy
Students Research Committee, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.


| Nasrin Panahi
2Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran. 2Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.


| Nima Razzaghi-Asl


نشانی اینترنتی http://rps.mui.ac.ir/index.php/jrps/article/view/2208
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زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article
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