Kazemi Farnoosh, Karimi Isaac, Yousofvand Namdar
Department of Biology, Faculty of Sciences, University of Razi, 67149-67346 Kermanshah, Iran.
In Silico Pharmacol. 2021 Jan 3;9(1):6. doi: 10.1007/s40203-020-00066-7. eCollection 2021.
P-glycoprotein (P-gp), which was first identified in cancer cells, is an ATP-dependent efflux transporter that expels a wide variety of cytotoxic compounds out of cells. This transporter can decrease the bioavailability of therapeutic drugs by preventing their sufficient intracellular accumulation. Over expression of P-gp in cancer cells lead to multidrug resistance (MDR) phenotype that is one of the main reasons for the failure of chemotherapy. Hence, P-gp inhibition is a favorable method to reverse MDR. In this study, the lignanamides from were docked against P-gp to recognize potential binding affinities of these phytochemicals. Tariquidar and zosuquidar, two well-known P-gp inhibitors, were selected as the control ligands. It was observed that cannabisin M and cannabisin N exhibited higher binding affinities (- 10.2 kcal/mol) to drug-binding pocket of P-gp when compared with tariquidar and zosuquidar that showed binding affinities of - 10.1 and - 9.6 kcal/mol, respectively. Based on these findings, cannabisin M and cannabisin N could be good drug candidates against P-gp.
P-糖蛋白（P-gp）最早在癌细胞中被发现，是一种依赖ATP的外排转运蛋白，可将多种细胞毒性化合物排出细胞。这种转运蛋白可通过阻止治疗药物在细胞内充分蓄积来降低其生物利用度。癌细胞中P-糖蛋白的过度表达会导致多药耐药（MDR）表型，这是化疗失败的主要原因之一。因此，抑制P-糖蛋白是逆转多药耐药的一种有效方法。在本研究中，将来自[具体来源未提及]的木脂酰胺与P-糖蛋白对接，以识别这些植物化学物质的潜在结合亲和力。选择两种著名的P-糖蛋白抑制剂他林洛尔和唑尼沙胺作为对照配体。结果发现，与他林洛尔和唑尼沙胺相比，大麻素M和大麻素N对P-糖蛋白的药物结合口袋表现出更高的结合亲和力（-10.2千卡/摩尔），他林洛尔和唑尼沙胺的结合亲和力分别为-10.1和-9.6千卡/摩尔。基于这些发现，大麻素M和大麻素N可能是对抗P-糖蛋白的良好候选药物。
