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Molecular docking study of lignanamides from Cannabis sativa against P-glycoprotein

Abstract

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 Cannabis sativa 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.

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Correspondence to Farnoosh Kazemi.

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Kazemi, F., Karimi, I. & Yousofvand, N. Molecular docking study of lignanamides from Cannabis sativa against P-glycoprotein. In Silico Pharmacol. 9, 6 (2021). https://doi.org/10.1007/s40203-020-00066-7

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  • DOI: https://doi.org/10.1007/s40203-020-00066-7

Keywords

  • P-glycoprotein
  • ABC transporter
  • Cannabis
  • Lignanamide
  • Molecular docking