Synthesis and biological evaluation of 2,5-disubstituted furan derivatives as P-glycoprotein inhibitors for Doxorubicin resistance in MCF-7/ADR cell

Li, Yasheng; Zhao, Dongsheng; Liu, Xingyu; Liao, Yixian; Jin, Hongwei; Song, Gaopeng; Cui, Zi‐Ning

doi:10.1016/j.ejmech.2018.04.012

Cited by 34 publications

(16 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although several compounds showed potent and selective efficacy for the P-gp transporter, only four compounds (14, 87 The mechanism of MDR modulation of all of the abovementioned compounds was due to an inhibition of P-gp-mediated drug efflux. 84,85,87,89 In addition, 16 inhibited P-gp ATPase activity without affecting P-gp expression. 84 In silico analyses, such as molecular docking and dynamic stimulation, indicated that 16 formed a long-lasting interaction with P-gp via hydrophobic interactions and hydrogen bond contacts.…”

Section: Compounds With a Tetrahydroisoquinoline Scaffoldmentioning

confidence: 96%

“…84 In silico analyses, such as molecular docking and dynamic stimulation, indicated that 16 formed a long-lasting interaction with P-gp via hydrophobic interactions and hydrogen bond contacts. 85,87 The in vivo pharmacokinetics of 16 alone, as well as DOX co-administrated with 16, indicated that 16 had a good oral bioavailability and did not significantly alter DOX metabolism. However, the in vivo P-gp-mediated MDR reversal efficacy of compounds in this class remains to be determined.…”

Section: Compounds With a Tetrahydroisoquinoline Scaffoldmentioning

confidence: 99%

“…The 6,7-dimethoxylated tetrahydroisoquinoline scaffold was the important pharmacophore that was nearly Apart from the tariquidar analogs, a series of tetrahydroisoquinoline-based P-gp inhibitors, with relatively simplified structures, have been reported 57,60,61,[84][85][86][87][88][89] and the general structure was characterized by connecting the important pharmacophore 6,7-dimethoxy-tetrahydroisoquinoline to an aromatic moiety by a flexible linker ( Figure 4A). After determining the P-gp inhibitory efficacy of these compounds in vitro, the general SAR studies of these compounds ( Figure 4A) indicated that the aromatic moiety is flexible and appropriate substitution on the aromatic ring could increase the efficacy.…”

Section: Compounds With a Tetrahydroisoquinoline Scaffoldmentioning

confidence: 99%

“…15,85 16,84 and 17,89 Figure 4B) were found to reverse P-gp-mediated MDR in cancer cells. Specifically, -gp inhibitor, elacridar 53.…”

mentioning

confidence: 97%

See 3 more Smart Citations

Chemical molecular‐based approach to overcome multidrug resistance in cancer by targeting P‐glycoprotein (P‐gp)

Zhang

Ashby

et al. 2020

Medicinal Research Reviews

185

View full text Add to dashboard Cite

Multidrug resistance (MDR) remains one of the major impediments for efficacious cancer chemotherapy. Increased efflux of multiple chemotherapeutic drugs by transmembrane ATP‐binding cassette (ABC) transporter superfamily is considered one of the primary causes for cancer MDR, in which the role of P‐glycoprotein (P‐gp/ABCB1) has been most well‐established. The clinical co‐administration of P‐gp drug efflux inhibitors, in combination with anticancer drugs which are P‐gp transport substrates, was considered to be a treatment modality to surmount MDR in anticancer therapy by blocking P‐gp‐mediated multidrug efflux. Extensive attempts have been carried out to screen for sets of nontoxic, selective, and efficacious P‐gp efflux inhibitors. In this review, we highlight the recent achievements in drug design, characterization, structure–activity relationship (SAR) studies, and mechanisms of action of the newly synthetic, potent small molecules P‐gp inhibitors in the past 5 years. The development of P‐gp inhibitors will increase our knowledge of the mechanisms and functions of P‐gp‐mediated drug efflux which will benefit drug discovery and clinical cancer therapeutics where P‐gp transporter overexpression has been implicated in MDR.

show abstract

Section: Compounds With a Tetrahydroisoquinoline Scaffoldmentioning

confidence: 96%

Section: Compounds With a Tetrahydroisoquinoline Scaffoldmentioning

confidence: 99%

Section: Compounds With a Tetrahydroisoquinoline Scaffoldmentioning

confidence: 99%

“…15,85 16,84 and 17,89 Figure 4B) were found to reverse P-gp-mediated MDR in cancer cells. Specifically, -gp inhibitor, elacridar 53.…”

mentioning

confidence: 97%

See 2 more Smart Citations

Chemical molecular‐based approach to overcome multidrug resistance in cancer by targeting P‐glycoprotein (P‐gp)

Zhang

Ashby

et al. 2020

Medicinal Research Reviews

185

View full text Add to dashboard Cite

show abstract

“…A number of small molecule inhibitors such as imatinib, nilotinib, and erlotinib have been reported to increase the intracellular accumulation of substrate drugs and reverse ABCB1-mediated MDR [1,4,5,8,11,12,13,17]. Recently, a number of studies have reported that antibiotics could reverse ABC transporters-mediated MDR [19,20,21,22,23]. In the light of such evidences, we investigated if ciprofloxacin could reverse ABCB1-mediated MDR.…”

Section: Introductionmentioning

confidence: 99%

Ciprofloxacin Enhances the Chemosensitivity of Cancer Cells to ABCB1 Substrates

Gupta

Gao

Ashar

et al. 2019

IJMS

View full text Add to dashboard Cite

ABCB1 is one of the major drug efflux transporters that is known to cause multidrug resistance (MDR) in cancer patients receiving chemotherapy for the treatment of solid tumors and hematological malignancies. Inhibition of ABCB1 efflux function is important for maintaining the intracellular concentration of chemotherapeutic drugs. Here, we evaluated ciprofloxacin for its ability to reverse MDR caused by the overexpression of ABCB1. Cytotoxicity of ciprofloxacin was determined by the MTT assay. The chemosensitizing effects of ciprofloxacin were determined in combination with ABCB1 substrates. The intracellular accumulation and efflux of ABCB1 substrates was measured by a scintillation counter, and protein expression was determined by the Western blotting. Vanadate-sensitive ATPase assay was performed to determine the effect of ciprofloxacin on the ATPase activity of ABCB1, and docking analysis was done to determine the interaction of ciprofloxacin with ABCB1. Ciprofloxacin significantly potentiated the cytotoxic effects of ABCB1 substrates in ABCB1-overexpressing cells. Furthermore, ciprofloxacin increased the intracellular accumulation and decreased the efflux of [3H]-paclitaxel without altering the expression of ABCB1. Ciprofloxacin stimulated the ATPase activity of ABCB1 in a concentration-dependent manner. Our findings showed that ciprofloxacin potently inhibits the ABCB1 efflux function and it has potential to be developed as a combination anticancer therapy.

show abstract

Chalcone hybrids as potential anticancer agents: Current development, mechanism of action, and structure‐activity relationship

Gao

Huang

Xiao

2020

Medicinal Research Reviews

View full text Add to dashboard Cite

The continuous emergency of drug‐resistant cancers and the low specificity of anticancer agents have been the major challenges in the control and treatment of cancer, making an urgent need to develop novel anticancer agents with high efficacy. Chalcones, precursors of flavonoids and isoflavonoids, exhibit structural heterogeneity and can act on various drug targets. Chalcones which demonstrated potential in vitro and in vivo activity against both drug‐susceptible and drug‐resistant cancers, are useful templates for the development of novel anticancer agents. Hybridization of chalcone moiety with other anticancer pharmacophores could provide the hybrids which have the potential to overcome drug resistance and improve the specificity, so it represents a promising strategy to develop novel anticancer agents. This review emphasizes the development, the mechanisms of action as well as structure‐activity relationships of chalcone hybrids with potential therapeutic application for many cancers in recent 10 years.

show abstract

Synthesis and biological evaluation of 2,5-disubstituted furan derivatives as P-glycoprotein inhibitors for Doxorubicin resistance in MCF-7/ADR cell

Cited by 34 publications

References 40 publications

Chemical molecular‐based approach to overcome multidrug resistance in cancer by targeting P‐glycoprotein (P‐gp)

Chemical molecular‐based approach to overcome multidrug resistance in cancer by targeting P‐glycoprotein (P‐gp)

Ciprofloxacin Enhances the Chemosensitivity of Cancer Cells to ABCB1 Substrates

Chalcone hybrids as potential anticancer agents: Current development, mechanism of action, and structure‐activity relationship

Contact Info

Product

Resources

About