2020
DOI: 10.1021/acs.jcim.0c00892
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(+/−)-Borneol Reverses Mitoxantrone Resistance against P-Glycoprotein

Abstract: P-Glycoprotein (Pgp) is a main factor contributing to multidrug resistance and the consequent failure of chemotherapy. Overcoming Pgp efflux is a strategy to improve the efficacy of drugs. (+)-Borneol (BNL1) and (−)-borneol (BNL2) interfere and inhibit Pgp, and thus, the accumulation of drugs increases in cells. However, it is not clear yet how they play the inhibitory effect against Pgp. In this work, the effect and molecular mechanism of borneol enantiomers in reversing mitoxantrone (MTO) resistance against … Show more

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Cited by 8 publications
(7 citation statements)
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“…Yang et al [ 79 ] reported that (+)-borneol (BNL1) and (-)-borneol (BNL2) can induce drug accumulation in cells due to its interference with P-glycoprotein (Pgp), an efflux protein that contributes to multidrug resistance to antibiotics and anticancer drugs, which could potentially explain the synergistic effects observed from the association between monoterpenes and antibiotics, as demonstrated in this work.…”
Section: Resultsmentioning
confidence: 67%
See 1 more Smart Citation
“…Yang et al [ 79 ] reported that (+)-borneol (BNL1) and (-)-borneol (BNL2) can induce drug accumulation in cells due to its interference with P-glycoprotein (Pgp), an efflux protein that contributes to multidrug resistance to antibiotics and anticancer drugs, which could potentially explain the synergistic effects observed from the association between monoterpenes and antibiotics, as demonstrated in this work.…”
Section: Resultsmentioning
confidence: 67%
“…Besides the antibacterial activity, research has demonstrated that borneol has analgesic, anti-inflammatory, antioxidant, healing, and antifungal activities [ 78 , 79 ].…”
Section: Resultsmentioning
confidence: 99%
“…Performed molecular docking studies demonstrated that all evaluated triterpenoids could properly fit into the transmembrane domain of the listed transporters with low binding energies, forming hydrogen bonds with key amino acid residues crucial for the pump activity of these proteins ( Figure 2 D): In the case of P-glycoprotein, SM and αO-SM formed a hydrogen bond with Tyr307, which is involved in regulating the ATP hydrolytic activity of the protein [ 36 ] and is a major interaction partner of the novel benzophenone sulfonamide-based inhibitor of P-glycoprotein [ 37 ]. The binding pockets of SM and SM epoxides were also found to involve a hydrogen bond with Gln347, which is a well-known inhibitor-binding residue in P-glycoprotein [ 38 , 39 , 40 ]. In the case of MRP1, αO-SM formed a hydrogen bond with Arg1248, playing an important function in the positioning of substrates within the drug-binding pocket of the protein [ 41 , 42 ] and involving the amino acid interaction network of the novel flavonoid-based inhibitor of MRP1 [ 43 ].…”
Section: Resultsmentioning
confidence: 99%
“…In the case of P-glycoprotein, SM and αO-SM formed a hydrogen bond with Tyr307, which is involved in regulating the ATP hydrolytic activity of the protein [ 36 ] and is a major interaction partner of the novel benzophenone sulfonamide-based inhibitor of P-glycoprotein [ 37 ]. The binding pockets of SM and SM epoxides were also found to involve a hydrogen bond with Gln347, which is a well-known inhibitor-binding residue in P-glycoprotein [ 38 , 39 , 40 ].…”
Section: Resultsmentioning
confidence: 99%
“…The intrinsic dynamic properties of the ligand‐binding pockets of proteins are important for the protein function mechanism 34 . Co‐administration with borneol can reduce the binding affinity between mitoxantrone and Pgp, as borneol prefers to bind the ligand‐binding pocket rather than the nucleotide‐binding domain of inward‐facing Pgp 35 . In summary, borneol has the potential to adjust the function of Pgp and increase the bioavailability of other drugs in the brain.…”
Section: Principle and Mechanism Of Penetration Of Borneol In The Brainmentioning
confidence: 99%