Flavonoid derivatives as selective ABCC1 modulators: Synthesis and functional characterization

Obreque-Balboa, José Esteban; Sun, Qiu; Bernhardt, Günther; König, Burkhard; Buschauer, Armin

doi:10.1016/j.ejmech.2015.12.010

Cited by 34 publications

(20 citation statements)

References 61 publications

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“…61,62 Compound 52 was also synthesized by another group as a reference compound due to its structural similarity to flavonoid derivatives being selective ABCC1 modulators. 63 Interestingly, the potency of compound 52 determined with MCF-7/Topo cells (IC 50 1.8 μM, I max 108%, Hoechst 33342 assay, FTC, 82 was used as reference at 10 μM) was tenfold lower than reported for the transfected HEK293 cells. The authors stated that the compound is selective for ABCG2, but mentioned that compound 52 stimulates ABCB1-mediated drug efflux activity at high concentrations.…”

Section: Chromonesmentioning

confidence: 86%

“…The effect of many flavonoids at 50 μM was comparable to 1 μM Ko143 (85). IC 50 values were determined for compounds exhibiting a significant inhibition of MTX transport, and seven flavonoids (apigenin [53], chrysoeriol [56], diosmetin [57], kaempferol [72], myricetin 3',4',5'-trimethylether [76], tamarixetin [78] and tricetin 3',4',5'-trimethylether [63]; Fig. 6), were found to have IC 50 values below 0.1 μM and in the same range as the reference compound Ko143 (0.026 ± 0.003 μM).…”

Section: Flavones Isoflavones Flavanones Flavonols and Rotenoidsmentioning

confidence: 99%

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ABCG2/BCRP: Specific and Nonspecific Modulators

Peña-Solórzano

Stark

König

et al. 2016

Medicinal Research Reviews

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Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2). The first two transporters have been widely studied already and reviews summarized the results. The ABCG2 protein has been a subject of intense study since its discovery as its overexpression has been detected in resistant cell lines in numerous types of human cancers. To date, a long list of modulators of ABCG2 exists and continues to increase. However, little is known about the clinical consequences of ABCG2 modulation. This makes the design of novel, potent, and nontoxic inhibitors of this efflux protein a major challenge to reverse MDR and thereby increase the success of chemotherapy. The aim of the present review is to describe and highlight specific and nonspecific modulators of ABCG2 reported to date based on the selectivity of the compounds, as many of them are effective against one or more ABC transport proteins.

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Section: Chromonesmentioning

confidence: 86%

Section: Flavones Isoflavones Flavanones Flavonols and Rotenoidsmentioning

confidence: 99%

ABCG2/BCRP: Specific and Nonspecific Modulators

Peña-Solórzano

Stark

König

et al. 2016

Medicinal Research Reviews

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“…Regarding MRP1, a recent study revealed that chromone derivatives, bearing amino groups or N -substituted carboxamine functional groups ( Figure 5 D), displayed potent and selective inhibition of this efflux pump [ 92 ].…”

Section: Introductionmentioning

confidence: 99%

Overcoming Multidrug Resistance: Flavonoid and Terpenoid Nitrogen-Containing Derivatives as ABC Transporter Modulators

2020

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Multidrug resistance (MDR) in cancer is one of the main limitations for chemotherapy success. Numerous mechanisms are behind the MDR phenomenon wherein the overexpression of the ATP-binding cassette (ABC) transporter proteins P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance protein 1 (MRP1) is highlighted as a prime factor. Natural product-derived compounds are being addressed as promising ABC transporter modulators to tackle MDR. Flavonoids and terpenoids have been extensively explored in this field as mono or dual modulators of these efflux pumps. Nitrogen-bearing moieties on these scaffolds were proved to influence the modulation of ABC transporters efflux function. This review highlights the potential of semisynthetic nitrogen-containing flavonoid and terpenoid derivatives as candidates for the design of effective MDR reversers. A brief introduction concerning the major role of efflux pumps in multidrug resistance, the potential of natural product-derived compounds in MDR reversal, namely natural flavonoid and terpenoids, and the effect of the introduction of nitrogen-containing groups are provided. The main modifications that have been performed during last few years to generate flavonoid and terpenoid derivatives, bearing nitrogen moieties, such as aliphatic, aromatic and heterocycle amine, amide, and related functional groups, as well as their P-gp, MRP1 and BCRP inhibitory activities are reviewed and discussed.

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“…Firstly, 2-ethylthio-4 H- thiochromen-4-one 1 was readily prepared from 2’-chloroacetophenone as the starting material through treatment with carbon disulfide in the presence of sodium hydride [23], followed by alkylation using iodoethane according to the literature procedures [13,16–17 19]. The oxidation of 1 with 1.2 or 5 equiv of H 2 O 2 yielded ethyl sulfoxide 2 and ethyl sulfone 3 , respectively (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

Wu¹,

Zhang²,

Ma³

et al. 2019

Beilstein J. Org. Chem.

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A highly efficient and convenient protocol was developed to access 2-amino-4H-benzothiopyran-4-ones through a process of conjugated addition–elimination. The sulfinyl group was proved to be the optimum leaving group by thorough investigations on the elimination of sulfide, sulfinyl, and sulfonyl groups at the 2-position of benzothiopyranone. Most 2-aminobenzothiopyranones were obtained in good to excellent yields under refluxing in isopropanol within 36 h. This method is base-free and the substrate scope in terms of electronic properties of the substituents of the benzothiopyranone is broad. The ten grams scale-up synthesis of the representative compounds 4a and 4d was implemented to show the practical application of this reaction, which afforded the corresponding compounds in good yields and excellent chemical purity without requiring column chromatographical purification.

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Flavonoid derivatives as selective ABCC1 modulators: Synthesis and functional characterization

Cited by 34 publications

References 61 publications

ABCG2/BCRP: Specific and Nonspecific Modulators

ABCG2/BCRP: Specific and Nonspecific Modulators

Overcoming Multidrug Resistance: Flavonoid and Terpenoid Nitrogen-Containing Derivatives as ABC Transporter Modulators

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

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