نرگس, رجائی ، غزاله, ره گوی ، پناهی, نسرین ، رزاقی اصل, نیما (1402) آنالیز بیوانفورماتیک ترکیبات طبیعی با پتانسیل مهار P-gp و غلبه بر مقاومت دارویی. Research in Pharmaceutical Sciences ــ 18 (5). ص.ص.505-516. شاپا 1735-9414
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آدرس اینترنتی رسمی : https://journals.lww.com/rips/fulltext/2023/18050/...
عنوان انگليسی
Bioinformatic analysis of highly consumed phytochemicals as P-gp binders to overcome drug-resistance
خلاصه انگلیسی
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.
نوع سند : | مقاله |
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زبان سند : | انگلیسی |
نویسنده اول : | رجائی نرگس |
نویسنده : | ره گوی غزاله |
نویسنده : | نسرین پناهی |
نویسنده مسئول : | نیما رزاقی اصل |
ضریب تاثیر و نمایه مجلات: | IF: 2.1 Indexed in: Scopus ,ESCI, PubMed/PMC |
کلیدواژه ها (فارسی): | Cancer , Drug resistance , P-gp , Phytochemicals , Molecular docking |
کلیدواژه ها (انگلیسی): | سرطان ، مقاومت دارویی ، پی-گلیکو پروتئین ، ترکیبات طبیعی ، داکینگ مولکولی |
موضوعات : | QV فارماکولوژی > QV 744 شیمی دارویی |
بخش های دانشگاهی : | دانشکده داروسازی > بخش شیمی دارویی |
کد شناسایی : | 17404 |
ارائه شده توسط : | دکتر نیما رزاقی اصل |
ارائه شده در تاریخ : | 30 آذر 1402 10:16 |
آخرین تغییر : | 30 آذر 1402 10:16 |
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