Structural and functional aspects of P-glycoprotein and its inhibitors

被引:134
作者
Mollazadeh, Shirin [1 ,2 ]
Sahebkar, Amirhossein [2 ,3 ,4 ]
Hadizadeh, Farzin [1 ,2 ]
Behravan, Javad [2 ,4 ]
Arabzadeh, Sepideh [2 ]
机构
[1] Mashhad Univ Med Sci, Sch Pharm, Dept Med Chem, Mashhad, Iran
[2] Mashhad Univ Med Sci, Pharmaceut Technol Inst, Biotechnol Res Ctr, Mashhad, Iran
[3] Mashhad Univ Med Sci, Neurogen Inflammat Res Ctr, Mashhad, Iran
[4] Mashhad Univ Med Sci, Sch Pharm, Mashhad, Iran
关键词
Multidrug resistance; Drug transporter; P-glycoprotein; Inhibitor; MULTIDRUG-RESISTANCE; MOLECULAR DOCKING; 1,4-DIHYDROPYRIDINE DERIVATIVES; ATP HYDROLYSIS; BINDING SITES; IN-VITRO; LIGAND; MODULATION; MECHANISMS; FLAVONOIDS;
D O I
10.1016/j.lfs.2018.10.048
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
P-glycoprotein (P-gp) is a member of ATP-binding cassette (ABC) superfamily which extrudes chemotherapeutic agents out of the cell. Suppression of this efflux activity has been the subject of numerous attempts to develop P-gp inhibitors. The aim of this review is to present up-to-date information on the structural and functional aspects of P-gp and its known inhibitors. The data presented also provide some information on drug discovery approaches for candidate P-gp inhibitors. Nucleotide-binding domains (NBDs) and drug-binding domains (DBDs) have been extensively studied to gain more information about P-gp inhibition and it looks that the ATPase activity of this pump has been the most attractive target for designing inhibitors. Hydrophobic and p-p (aromatic) interactions between P-gp binding domains and inhibitors are dominant intermolecular forces that have been reported in many studies using different methods. Many synthetic and natural products have been found to possess inhibitory or modulatory effects on drug transporter proteins. Log P value is an important factor in studying these inhibitors and has a crucial role on absorption, distribution, metabolism, and excretion (ADME) properties of candidate P-gp inhibitors.
引用
收藏
页码:118 / 123
页数:6
相关论文
共 56 条
[1]   P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review [J].
Abdallah, Hossam M. ;
Al-Abd, Ahmed M. ;
El-Dine, Riham Salah ;
El-Halawany, Ali M. .
JOURNAL OF ADVANCED RESEARCH, 2015, 6 (01) :45-62
[2]  
[Anonymous], BIOCH BIOPHYS ACTA B
[3]  
Bahadur S., 2017, SYNERGY, V4, P1, DOI [10.1016/j.synres.2016.12.001, DOI 10.1016/J.SYNRES.2016.12.001]
[4]   Emerging Significance of Flavonoids as P-Glycoprotein Inhibitors in Cancer Chemotherapy [J].
Bansal, Tripta ;
Jaggi, Manu ;
Khar, Roop K. ;
Talegaonkar, Sushama .
JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, 2009, 12 (01) :46-78
[5]  
Barreto-Ojeda E., 2018, J GEN PHYSIOL
[6]   In Silico Screening for Inhibitors of P-Glycoprotein That Target the Nucleotide Binding Domains [J].
Brewer, Frances K. ;
Follit, Courtney A. ;
Vogel, Pia D. ;
Wise, John G. .
MOLECULAR PHARMACOLOGY, 2014, 86 (06) :716-726
[7]   Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein [J].
Chufan, Eduardo E. ;
Kapoor, Khyati ;
Ambudkar, Suresh V. .
BIOCHEMICAL PHARMACOLOGY, 2016, 101 :40-53
[8]   The reliability of molecular dynamics simulations of the multidrug transporter P-glycoprotein in a membrane environment [J].
Condic-Jurkic, Karmen ;
Subramanian, Nandhitha ;
Mark, Alan E. ;
O'Mara, Megan L. .
PLOS ONE, 2018, 13 (01)
[9]   Molecular Docking and P-glycoprotein Inhibitory Activity of Flavonoids [J].
Daddam, Jayasimha Rayalu ;
Dowlathabad, Muralidhara Rao ;
Panthangi, Seshapani ;
Jasti, Pramodakumari .
INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES, 2014, 6 (03) :167-175
[10]   Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters [J].
Di Pietro, A ;
Conseil, G ;
Pérez-Victoria, JM ;
Dayan, G ;
Baubichon-Cortay, H ;
Trompier, D ;
Steinfels, E ;
Jault, JM ;
de Wet, H ;
Maitrejean, M ;
Comte, G ;
Boumendjel, A ;
Mariotte, AM ;
Dumontet, C ;
McIntosh, DB ;
Goffeau, A ;
Castanys, S ;
Gamarro, F ;
Barron, D .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2002, 59 (02) :307-322