Abstract
The P-glycoprotein is an efflux transporter that expels substances out of the cells and has an important impact on the pharmacokinetic and pharmacodynamic properties of drugs. The study of the interactions between ligands and the P-glycoprotein has implications in the design of Central Nervous System drugs and their transport across the blood-brain barrier. Moreover, since the P-glycoprotein is overexpressed in some types of cancers, the protein is responsible for expelling the drug therapies from the cells, and hence, for drug resistance. In this review, we describe different P-glycoprotein binding sites reported for substrates, inhibitors and modulators, and focus on molecular docking studies that provide useful information about drugs and P-glycoprotein interactions. Docking in crystallized structures and homology models showed potential in the detection of the binding site and key residues responsible for ligand recognition. Moreover, virtual screening through molecular docking discriminates P-glycoprotein ligands from decoys. We also discuss challenges and limitations of molecular docking simulations applied to this particular protein. Computational structure-based approaches are very helpful in the study of novel ligands that interact with the P-glycoprotein and provide insights to understand the P-glycoprotein molecular mechanism of action.
Keywords: P-glycoprotein, homology modeling, molecular docking, blood-brain barrier, drug resistance, ANP.
[1]
Eckford, P.D.; Sharom, F.J. ABC efflux pump-based resistance to chemotherapy drugs. Chem. Rev., 2009, 109(7), 2989-3011.
[2]
Colmenarejo, G. in silico ADME Prediction. Data Sets and Models. Curr. Comput. Aided Drug Des., 2005, 1, 365-376.
[3]
Szakács, G.; Váradi, A.; Ozvegy-Laczka, C.; Sarkadi, B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discov. Today, 2008, 13(9-10), 379-393.
[4]
Kim, R.B.; Fromm, M.F.; Wandel, C.; Leake, B.; Wood, A.J.; Roden, D.M.; Wilkinson, G.R. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest., 1998, 101(2), 289-294.
[5]
Linnet, K.; Ejsing, T.B. A review on the impact of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs. Eur. Neuropsychopharmacol., 2008, 18(3), 157-169.
[6]
Colabufo, N.A.; Berardi, F.; Cantore, M.; Contino, M.; Inglese, C.; Niso, M.; Perrone, R. Perspectives of P-glycoprotein modulating agents in oncology and neurodegenerative diseases: pharmaceutical, biological, and diagnostic potentials. J. Med. Chem., 2010, 53(5), 1883-1897.
[7]
Schinkel, A.H.; Jonker, J.W. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv. Drug Deliv. Rev., 2003, 55(1), 3-29.
[8]
Kim, R.B. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab. Rev., 2002, 34(1-2), 47-54.
[9]
Colabufo, N.A.; Berardi, F.; Perrone, M.G.; Capparelli, E.; Cantore, M.; Inglese, C.; Perrone, R. Substrates, inhibitors and activators of P-glycoprotein: candidates for radiolabeling and imaging perspectives. Curr. Top. Med. Chem., 2010, 10(17), 1703-1714.
[10]
Chen, L.; Li, Y.; Yu, H.; Zhang, L.; Hou, T. Computational models for predicting substrates or inhibitors of P-glycoprotein. Drug Discov. Today, 2012, 17(7-8), 343-351.
[11]
Silva, R.; Vilas-Boas, V.; Carmo, H.; Dinis-Oliveira, R.J.; Carvalho, F.; de Lourdes Bastos, M.; Remião, F. Modulation of P-glycoprotein efflux pump: induction and activation as a therapeutic strategy. Pharmacol. Ther., 2015, 149, 1-123.
[12]
Geick, A.; Eichelbaum, M.; Burk, O. Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J. Biol. Chem., 2001, 276(18), 14581-14587.
[13]
Thomas, H.; Coley, H.M. Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Contr., 2003, 10(2), 159-165.
[14]
Callaghan, R.; Luk, F.; Bebawy, M. Inhibition of the multidrug resistance P-glycoprotein: time for a change of strategy? Drug Metab. Dispos., 2014, 42(4), 623-631.
[15]
Oldham, M.L.; Davidson, A.L.; Chen, J. Structural insights into ABC transporter mechanism. Curr. Opin. Struct. Biol., 2008, 18(6), 726-733.
[16]
Locher, K.P. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat. Struct. Mol. Biol., 2016, 23(6), 487-493.
[17]
Altenberg, G.A.; Vanoye, C.G.; Horton, J.K.; Reuss, L. Unidirectional fluxes of rhodamine 123 in multidrug-resistant cells: evidence against direct drug extrusion from the plasma membrane. Proc. Natl. Acad. Sci. USA, 1994, 91(11), 4654-4657.
[18]
Higgins, C.F.; Gottesman, M.M. Is the multidrug transporter a flippase? Trends Biochem. Sci., 1992, 17(1), 18-21.
[19]
Raviv, Y.; Pollard, H.B.; Bruggemann, E.P.; Pastan, I.; Gottesman, M.M. Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells. J. Biol. Chem., 1990, 265(7), 3975-3980.
[20]
Ekins, S.; Ecker, G.F.; Chiba, P.; Swaan, P.W. Future directions for drug transporter modelling. Xenobiotica, 2007, 37(10-11), 1152-1170.
[21]
Cui, Y.; Chen, Q.; Li, Y.; Tang, L. A new model of flavonoids affinity towards P-glycoprotein: genetic algorithm-support vector machine with features selected by a modified particle swarm optimization algorithm. Arch. Pharm. Res., 2017, 40(2), 214-230.
[22]
Miyata, K.; Nakagawa, Y.; Kimura, Y.; Ueda, K.; Akamatsu, M. Structure-activity relationships of dibenzoylhydrazines for the inhibition of P-glycoprotein-mediated quinidine transport. Bioorg. Med. Chem., 2016, 24(14), 3184-3191.
[23]
Sousa, I.J.; Ferreira, M.J.; Molnár, J.; Fernandes, M.X. QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity. Eur. J. Pharm. Sci., 2013, 48(3), 542-553.
[25]
AlQudah, D.A.; Zihlif, M.A.; Taha, M.O. Ligand-based modeling of diverse aryalkylamines yields new potent P-glycoprotein inhibitors. Eur. J. Med. Chem., 2016, 110, 204-223.
[26]
Ferreira, R.J.; dos Santos, D.J.; Ferreira, M.J.; Guedes, R.C. Toward a better pharmacophore description of P-glycoprotein modulators, based on macrocyclic diterpenes from Euphorbia species. J. Chem. Inf. Model., 2011, 51(6), 1315-1324.
[27]
Li, W.X.; Li, L.; Eksterowicz, J.; Ling, X.B.; Cardozo, M. Significance analysis and multiple pharmacophore models for differentiating P-glycoprotein substrates. J. Chem. Inf. Model., 2007, 47(6), 2429-2438.
[28]
Ha, S.N.; Hochman, J.; Sheridan, R.P. Mini review on molecular modeling of P-glycoprotein (Pgp). Curr. Top. Med. Chem., 2007, 7(15), 1525-1529.
[29]
Liu, H.; Ma, Z.; Wu, B. Structure-activity relationships and in silico models of P-glycoprotein (ABCB1) inhibitors. Xenobiotica, 2013, 43(11), 1018-1026.
[30]
Palmeira, A.; Sousa, E.; Vasconcelos, M.H.; Pinto, M.; Fernandes, M.X. Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective. Curr. Pharm. Des., 2012, 18(27), 4197-4214.
[31]
Demel, M.A.; Schwaha, R.; Krämer, O.; Ettmayer, P.; Haaksma, E.E.; Ecker, G.F. in silico prediction of substrate properties for ABC-multidrug transporters. Expert Opin. Drug Metab. Toxicol., 2008, 4(9), 1167-1180.
[32]
Montanari, F.; Ecker, G.F. Prediction of drug-ABC-transporter interaction--recent advances and future challenges. Adv. Drug Deliv. Rev., 2015, 86, 17-26.
[33]
Pinto, M.; Digles, D.; Ecker, G.F. Computational models for predicting the interaction with ABC transporters. Drug Discov. Today. Technol., 2014, 12, e69-e77.
[34]
Rajput, A.H. Environmental toxins accelerate Parkinson’s disease onset. Neurology, 2001, 56(1), 4-5.
[35]
Vogelgesang, S.; Cascorbi, I.; Schroeder, E.; Pahnke, J.; Kroemer, H.K.; Siegmund, W.; Kunert-Keil, C.; Walker, L.C.; Warzok, R.W. Deposition of Alzheimer’s beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenetics, 2002, 12(7), 535-541.
[36]
Kuhnke, D.; Jedlitschky, G.; Grube, M.; Krohn, M.; Jucker, M.; Mosyagin, I.; Cascorbi, I.; Walker, L.C.; Kroemer, H.K.; Warzok, R.W.; Vogelgesang, S. MDR1-P-Glycoprotein (ABCB1) Mediates Transport of Alzheimer’s amyloid-beta peptides--implications for the mechanisms of Abeta clearance at the blood-brain barrier. Brain Pathol., 2007, 17(4), 347-353.
[37]
Banks, W.A. Characteristics of compounds that cross the blood-brain barrier. BMC Neurol., 2009, 9(Suppl. 1), S3.
[38]
Lin, J.H.; Yamazaki, M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet., 2003, 42(1), 59-98.
[39]
Lehne, G. P-glycoprotein as a drug target in the treatment of multidrug resistant cancer. Curr. Drug Targets, 2000, 1(1), 85-99.
[40]
Aller, S.G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R.; Harrell, P.M.; Trinh, Y.T.; Zhang, Q.; Urbatsch, I.L.; Chang, G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science, 2009, 323(5922), 1718-1722.
[41]
Jin, M.S.; Oldham, M.L.; Zhang, Q.; Chen, J. Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature, 2012, 490(7421), 566-569.
[42]
Ward, A.B.; Szewczyk, P.; Grimard, V.; Lee, C.W.; Martinez, L.; Doshi, R.; Caya, A.; Villaluz, M.; Pardon, E.; Cregger, C.; Swartz, D.J.; Falson, P.G.; Urbatsch, I.L.; Govaerts, C.; Steyaert, J.; Chang, G. Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain. Proc. Natl. Acad. Sci. USA, 2013, 110(33), 13386-13391.
[43]
Li, J.; Jaimes, K.F.; Aller, S.G. Refined structures of mouse P-glycoprotein. Protein Sci., 2014, 23(1), 34-46.
[44]
Szewczyk, P.; Tao, H.; McGrath, A.P.; Villaluz, M.; Rees, S.D.; Lee, S.C.; Doshi, R.; Urbatsch, I.L.; Zhang, Q.; Chang, G. Snapshots of ligand entry, malleable binding and induced helical movement in P-glycoprotein. Acta Crystallogr. D Biol. Crystallogr., 2015, 71(Pt 3), 732-741.
[45]
Tombline, G.; Muharemagić, A.; White, L.B.; Senior, A.E. Involvement of the “occluded nucleotide conformation” of P-glycoprotein in the catalytic pathway. Biochemistry, 2005, 44(38), 12879-12886.
[46]
Loo, T.W.; Bartlett, M.C.; Clarke, D.M. Simultaneous binding of two different drugs in the binding pocket of the human multidrug resistance P-glycoprotein. J. Biol. Chem., 2003, 278(41), 39706-39710.
[47]
Ferreira, R.J.; Ferreira, M.J.; dos Santos, D.J. Molecular docking characterizes substrate-binding sites and efflux modulation mechanisms within P-glycoprotein. J. Chem. Inf. Model., 2013, 53(7), 1747-1760.
[48]
Shapiro, A.B.; Ling, V. Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities. Eur. J. Biochem., 1997, 250(1), 130-137.
[49]
Shapiro, A.B.; Ling, V. Transport of LDS-751 from the cytoplasmic leaflet of the plasma membrane by the rhodamine-123-selective site of P-glycoprotein. Eur. J. Biochem., 1998, 254(1), 181-188.
[50]
Pleban, K.; Kopp, S.; Csaszar, E.; Peer, M.; Hrebicek, T.; Rizzi, A.; Ecker, G.F.; Chiba, P. P-glycoprotein substrate binding domains are located at the transmembrane domain/transmembrane domain interfaces: a combined photoaffinity labeling-protein homology modeling approach. Mol. Pharmacol., 2005, 67(2), 365-374.
[51]
Martinez, L.; Arnaud, O.; Henin, E.; Tao, H.; Chaptal, V.; Doshi, R.; Andrieu, T.; Dussurgey, S.; Tod, M.; Di Pietro, A.; Zhang, Q.; Chang, G.; Falson, P. Understanding polyspecificity within the substrate-binding cavity of the human multidrug resistance P-glycoprotein. FEBS J., 2014, 281(3), 673-682.
[52]
Conseil, G.; Baubichon-Cortay, H.; Dayan, G.; Jault, J.M.; Barron, D.; Di Pietro, A. Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP- and steroid-binding sites on mouse P-glycoprotein. Proc. Natl. Acad. Sci. USA, 1998, 95(17), 9831-9836.
[53]
Dayan, G.; Jault, J.M.; Baubichon-Cortay, H.; Baggetto, L.G.; Renoir, J.M.; Baulieu, E.E.; Gros, P.; Di Pietro, A. Binding of steroid modulators to recombinant cytosolic domain from mouse P-glycoprotein in close proximity to the ATP site. Biochemistry, 1997, 36(49), 15208-15215.
[54]
Georges, E.; Tsuruo, T.; Ling, V. Topology of P-glycoprotein as determined by epitope mapping of MRK-16 monoclonal antibody. J. Biol. Chem., 1993, 268(3), 1792-1798.
[55]
Vilas-Boas, V.; Silva, R.; Nunes, C.; Reis, S.; Ferreira, L.; Vieira, C.; Carvalho, F. Bastos, Mde, L.; Remião, F. Mechanisms of P-gp inhibition and effects on membrane fluidity of a new rifampicin derivative, 1,8-dibenzoyl-rifampicin. Toxicol. Lett., 2013, 220(3), 259-266.
[56]
Regev, R.; Assaraf, Y.G.; Eytan, G.D. Membrane fluidization by ether, other anesthetics, and certain agents abolishes P-glycoprotein ATPase activity and modulates efflux from multidrug-resistant cells. Eur. J. Biochem., 1999, 259(1-2), 18-24.
[57]
Dawson, R.J.; Locher, K.P. Structure of a bacterial multidrug ABC transporter. Nature, 2006, 443(7108), 180-185.
[58]
Zolnerciks, J.K.; Wooding, C.; Linton, K.J. Evidence for a Sav1866-like architecture for the human multidrug transporter P-glycoprotein. FASEB J., 2007, 21(14), 3937-3948.
[59]
Pajeva, I.K.; Globisch, C.; Wiese, M. Combined pharmacophore modeling, docking, and 3D QSAR studies of ABCB1 and ABCC1 transporter inhibitors. ChemMedChem, 2009, 4(11), 1883-1896.
[61]
Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[62]
Ferreira, R.J.; Ferreira, M.J.; Dos Santos, D.J. Insights on p-glycoprotein’s efflux mechanism obtained by molecular dynamics simulations. J. Chem. Theory Comput., 2012, 8(6), 1853-1864.
[63]
Chen, C.Y.; Lin, C.M.; Lin, H.C.; Huang, C.F.; Lee, C.Y.; Si Tou, T.C.; Hung, C.C.; Chang, C.S. Structure-activity relationship study of novel 2-aminobenzofuran derivatives as P-glycoprotein inhibitors. Eur. J. Med. Chem., 2017, 125, 1023-1035.
[64]
Zeino, M.; Saeed, M.E.; Kadioglu, O.; Efferth, T. The ability of molecular docking to unravel the controversy and challenges related to P-glycoprotein-a well-known, yet poorly understood drug transporter. Invest. New Drugs, 2014, 32(4), 618-625.
[65]
Kumar, R.; Kaur, M.; Bahia, M.S.; Silakari, O. Synthesis, cytotoxic study and docking based multidrug resistance modulator potential analysis of 2-(9-oxoacridin-10(9H)-yl)-N-phenyl acetamides. Eur. J. Med. Chem., 2014, 80, 83-91.
[66]
Murahari, M.; Kharkar, P.S.; Lonikar, N.; Mayur, Y.C. Design, synthesis, biological evaluation, molecular docking and QSAR studies of 2,4-dimethylacridones as anticancer agents. Eur. J. Med. Chem., 2017, 130, 154-170.
[67]
Dolghih, E.; Bryant, C.; Renslo, A.R.; Jacobson, M.P. Predicting binding to p-glycoprotein by flexible receptor docking. PLOS Comput. Biol., 2011, 7(6)e1002083
[68]
Schrödinger package, Schrödinger, LLC, New York, USA. Available at:
http://www.schrodinger.com/
[Accessed: Aug
30, 2017]
[69]
Shityakov, S.; Förster, C. in silico structure-based screening of versatile P-glycoprotein inhibitors using polynomial empirical scoring functions. Adv. Appl. Bioinform. Chem., 2014, 7, 1-9.
[70]
Warren, G.L.; Andrews, C.W.; Capelli, A.M.; Clarke, B.; LaLonde, J.; Lambert, M.H.; Lindvall, M.; Nevins, N.; Semus, S.F.; Senger, S.; Tedesco, G.; Wall, I.D.; Woolven, J.M.; Peishoff, C.E.; Head, M.S. A critical assessment of docking programs and scoring functions. J. Med. Chem., 2006, 49(20), 5912-5931.
[71]
Pan, L.; Hu, H.; Wang, X.; Yu, L.; Jiang, H.; Chen, J.; Lou, Y.; Zeng, S. Inhibitory effects of neochamaejasmin B on P-glycoprotein in MDCK-hMDR1 cells and molecular docking of NCB binding in P-glycoprotein. Molecules, 2015, 20(2), 2931-2948.
[72]
Ahmad, B.; Rizwan, M.; Rauf, A.; Raza, M.; Azam, S.; Bashir, S.; Molnar, J.; Csonka, A.; Szabo, D. Isolation and structure elucidation, molecular docking studies of screlotiumol from soil borne fungi Screlotium rolfsii and their reversal of multidrug resistance in mouse lymphoma cells. Asian Pac. J. Cancer Prev., 2016, 17(4), 2083-2087.
[73]
Shityakov, S.; Förster, C. Multidrug resistance protein P-gp interaction with nanoparticles (fullerenes and carbon nanotube) to assess their drug delivery potential: a theoretical molecular docking study. Int. J. Comput. Biol. Drug Des., 2013, 6(4), 343-357.
[74]
Shahraki, O.; Zargari, F.; Edraki, N.; Khoshneviszadeh, M.; Firuzi, O.; Miri, R. Molecular dynamics simulation and molecular docking studies of 1,4-Dihydropyridines as P-glycoprotein’s allosteric inhibitors. J. Biomol. Struct. Dyn., 2018, 36(1), 112-125.
[75]
Bikadi, Z.; Hazai, I.; Malik, D.; Jemnitz, K.; Veres, Z.; Hari, P.; Ni, Z.; Loo, T.W.; Clarke, D.M.; Hazai, E.; Mao, Q. Predicting P-glycoprotein-mediated drug transport based on support vector machine and three-dimensional crystal structure of P-glycoprotein. PLoS One, 2011, 6(10)e25815
[76]
Ngo, T.D.; Tran, T.D.; Le, M.T.; Thai, K.M. Computational predictive models for P-glycoprotein inhibition of in-house chalcone derivatives and drug-bank compounds. Mol. Divers., 2016, 20(4), 945-961.
[77]
Becker, J.P.; Depret, G.; Van Bambeke, F.; Tulkens, P.M.; Prévost, M. Molecular models of human P-glycoprotein in two different catalytic states. BMC Struct. Biol., 2009, 9, 3.
[78]
Ward, A.; Reyes, C.L.; Yu, J.; Roth, C.B.; Chang, G. Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc. Natl. Acad. Sci. USA, 2007, 104(48), 19005-19010.
[79]
Vilas-Boas, V.; Silva, R.; Palmeira, A.; Sousa, E.; Ferreira, L.M.; Branco, P.S.; Carvalho, F. Bastos, Mde.L.; Remião, F. Development of novel rifampicin-derived P-glycoprotein activators/inducers. synthesis, in silico analysis and application in the RBE4 cell model, using paraquat as substrate. PLoS One, 2013, 8(8)e74425
[80]
Silva, R.; Sousa, E.; Carmo, H.; Palmeira, A.; Barbosa, D.J.; Gameiro, M.; Pinto, M. Bastos, Mde, L.; Remião, F. Induction and activation of P-glycoprotein by dihydroxylated xanthones protect against the cytotoxicity of the P-glycoprotein substrate paraquat. Arch. Toxicol., 2014, 88(4), 937-951.
[81]
Palmeira, A.; Sousa, E.; Fernandes, M.X.; Pinto, M.M.; Vasconcelos, M.H. Multidrug resistance reversal effects of aminated thioxanthones and interaction with cytochrome P450 3A4. J. Pharm. Pharm. Sci., 2012, 15(1), 31-45.
[83]
Tan, W.; Mei, H.; Chao, L.; Liu, T.; Pan, X.; Shu, M.; Yang, L. Combined QSAR and molecule docking studies on predicting P-glycoprotein inhibitors. J. Comput. Aided Mol. Des., 2013, 27(12), 1067-1073.
[84]
Jabeen, I.; Pleban, K.; Rinner, U.; Chiba, P.; Ecker, G.F. Structure-activity relationships, ligand efficiency, and lipophilic efficiency profiles of benzophenone-type inhibitors of the multidrug transporter P-glycoprotein. J. Med. Chem., 2012, 55(7), 3261-3273.
[85]
Klepsch, F.; Chiba, P.; Ecker, G.F. Exhaustive sampling of docking poses reveals binding hypotheses for propafenone type inhibitors of P-glycoprotein. PLOS Comput. Biol., 2011, 7(5)e1002036
[86]
Sali, A.; Blundell, T.L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol., 1993, 234(3), 779-815.
[87]
GOLD. The Cambridge Crystallographic Data Centre
(CCDC). Available at:
https://www.ccdc.cam.ac.uk/ solutions/csd-discovery/components/gold/
[Accessed: Sep 15, 2017]
[88]
Kothandan, G.; Gadhe, C.G.; Madhavan, T.; Choi, C.H.; Cho, S.J. Docking and 3D-QSAR (quantitative structure activity relationship) studies of flavones, the potent inhibitors of p-glycoprotein targeting the nucleotide binding domain. Eur. J. Med. Chem., 2011, 46(9), 4078-4088.
[89]
Daddam, J.R.; Dowlathabad, M.R.; Panthangi, S.; Jasti, P. Molecular docking and P-glycoprotein inhibitory activity of flavonoids. Interdiscip. Sci., 2014, 6(3), 167-175.
[90]
Di Pietro, A.; Conseil, G.; Pérez-Victoria, J.M.; Dayan, G.; Baubichon-Cortay, H.; Trompier, D.; Steinfels, E.; Jault, J.M.; de Wet, H.; Maitrejean, M.; Comte, G.; Boumendjel, A.; Mariotte, A.M.; Dumontet, C.; McIntosh, D.B.; Goffeau, A.; Castanys, S.; Gamarro, F.; Barron, D. Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters. Cell. Mol. Life Sci., 2002, 59(2), 307-322.
[91]
Saeed, M.; Kadioglu, O.; Khalid, H.; Sugimoto, Y.; Efferth, T. Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking. J. Nutr. Biochem., 2015, 26(1), 44-56.
[92]
Kadioglu, O.; Saeed, M.E.; Valoti, M.; Frosini, M.; Sgaragli, G.; Efferth, T. Interactions of human P-glycoprotein transport substrates and inhibitors at the drug binding domain: Functional and molecular docking analyses. Biochem. Pharmacol., 2016, 104, 42-51.
[93]
Subhani, S.; Jayaraman, A.; Jamil, K. Homology modelling and molecular docking of MDR1 with chemotherapeutic agents in non-small cell lung cancer. Biomed. Pharmacother., 2015, 71, 37-45.
[94]
Palestro, P.H.; Gavernet, L.; Estiu, G.L.; Bruno Blanch, L.E. Docking applied to the prediction of the affinity of compounds to P-glycoprotein. BioMed Res. Int., 2014, 2014358425
[95]
Klepsch, F.; Vasanthanathan, P.; Ecker, G.F. Ligand and structure-based classification models for prediction of P-glycoprotein inhibitors. J. Chem. Inf. Model., 2014, 54(1), 218-229.
[97]
Kitchen, D.B.; Decornez, H.; Furr, J.R.; Bajorath, J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat. Rev. Drug Discov., 2004, 3(11), 935-949.
[98]
Cheng, T.; Li, Q.; Zhou, Z.; Wang, Y.; Bryant, S.H. Structure-based virtual screening for drug discovery: a problem-centric review. AAPS J., 2012, 14(1), 133-141.
[99]
Yuriev, E.; Holien, J.; Ramsland, P.A. Improvements, trends, and new ideas in molecular docking: 2012-2013 in review. J. Mol. Recognit., 2015, 28(10), 581-604.
[100]
Chaudhary, K.K.; Mishra, N. A Review on molecular docking: novel tool for drug discovery. JSM Chem., 2016, 4, 1029.
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