New, highly potent and non-toxic, chromone inhibitors of the human breast cancer resistance protein ABCG2

Pires, Amanda do Rocio Andrade; Lecerf-Schmidt, Florine; Guragossian, Nathalie; Pazinato, Jaqueline; Gozzi, Gustavo Jabor; Winter, Evelyn; Valdameri, Gláucio; Veale, Alexander; Boumendjel, Ahcène; Pietro, Attilio Di; Pérès, Basile

doi:10.1016/j.ejmech.2016.05.053

Cited by 27 publications

(13 citation statements)

References 23 publications

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“…The structurally unrelated benzothiazole-triazine derivative PZ-39 135 has also been found to be a non-toxic and specific ABCG2 inhibitor which also accelerates ABCG2 degradation [ 121 ] as has been shown for novobiocin [ 122 ] or the flavon 6-prenylchrysin [ 123 ]. Only recently the chromone derivative 136 has been reported as specific ABCG2 inhibitor with low toxicity [ 124 ] (Figure 9). A number of ABCG2 inhibitors have been described in patents but the available pharmacological data are too preliminary to predict the outcome of in vivo studies [ 125 ].…”

Section: Resultsmentioning

confidence: 92%

Fumitremorgins and Relatives – From Tremorgenic Compounds to Valuable Anti-Cancer Drugs

Abraham

2018

CMC

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Section: Resultsmentioning

confidence: 92%

Fumitremorgins and Relatives – From Tremorgenic Compounds to Valuable Anti-Cancer Drugs

Abraham

2018

CMC

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“…[ 17 , 18 , 19 ] As part of flavonoids, the chromones (4) have been widely studied and characterized as novel potent, selective and non‐toxic ABCG2 inhibitors. [ 20 , 21 ] Despite the increased number of ABCG2 studies, no inhibitor for clinical use is yet available. [ 14 , 22 , 23 ]…”

Section: Introductionmentioning

confidence: 99%

Tetrahydroquinoline/4,5‐Dihydroisoxazole Molecular Hybrids as Inhibitors of Breast Cancer Resistance Protein (BCRP/ABCG2)

et al. 2021

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Multidrug resistance (MDR) is one of the major factors in the failure of many chemotherapy approaches. In cancer cells, MDR is mainly associated with the expression of ABC transporters such as P-glycoprotein, MRP1 and ABCG2. Despite major efforts to develop new selective and potent inhibitors of ABC drug transporters, no ABCG2-specific inhibitors for clinical use are yet available. Here, we report the evaluation of sixteen tetrahydroquinoline/4,5-dihydroisoxazole derivatives as a new class of ABCG2 inhibitors. The affinity of the five best inhibitors was further investigated by the vanadate-sensitive ATPase assay. Molecular modelling data, proposing a potential binding mode, suggest that they can inhibit the ABCG2 activity by binding on site S1, previously reported as inhibitors binding region, as well targeting site S2, a selective region for substrates, and by specifically interacting with residues Asn436, Gln398, and Leu555. Altogether, this study provided new insights into THQ/ 4,5-dihydroisoxazole molecular hybrids, generating great potential for the development of novel most potent ABCG2 inhibitors.

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“…Substituted chromones represent one of the major classes of naturally occurring compounds . Chromones revealed variable biological activities including antimicrobial , antioxidant activity , anticancer , and neuroprotective . Chromone‐3‐carbonitriles have attracted significant consideration as highly reactive compounds, due to the presence of three electrophilic centers (C‐2, C‐4, and CN group) .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Density Functional Theory Band Structure Calculations, Optical, and Photoelectrical Characterizations of the Novel (9‐Bromo‐3‐cyano‐5‐oxo‐1,5‐dihydro‐2H‐chromeno[4,3‐b]pyridin‐2‐ylidene)propanedinitrile

Halim

Ibrahim

2019

Journal of Heterocyclic Chem

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Ring transformation of 6‐bromochromone‐3‐carbonitrile (1) with malononitrile dimer in basic medium furnished the unexpected (9‐bromo‐3‐cyano‐5‐oxo‐1,5‐dihydro‐2H‐chromeno[4,3‐b]pyridin‐2‐ylidene)propanedinitrile (2, BCOCPP). Density functional theory, theoretical investigation of the electronic structure, geometries linear polarizability ⟨Δα⟩ (Quadrupole moment), first‐order hyperpolarizability ⟨β⟩ (Octapole moment), natural bonding orbital, molecular electrostatic potential contours, thermo‐chemical parameters, harmonic vibration frequencies, the FT‐IR spectrum of the compound (2, BCOCPP) in the solid phase was recorded, and time‐dependent density functional theory calculations at the B3LYP/6‐311G (d,p) level of theory, UV‐Vis spectra, in both ethanol and dioxane solvents have been employed for compound (2, BCOCPP). The geometrical and energetic parameters have been extensively investigated to reveal the reason behind the selective formation of compound (2, BCOCPP), instead of expected product 3. The Coulomb‐attenuating method‐B3LYP and Corrected Linear Response Polarizable Continuum Model studied for theoretically obtaining the electronic absorption spectra in gas phase, ethanol, and dioxane, respectively, and indicate a good agreement with the observed spectra. The heterojunction based on BCOCPP showed phototransient properties under various illumination intensities that give the recommendation of the studied heterojunction in the field of optoelectronic device application.

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New, highly potent and non-toxic, chromone inhibitors of the human breast cancer resistance protein ABCG2

Cited by 27 publications

References 23 publications

Fumitremorgins and Relatives – From Tremorgenic Compounds to Valuable Anti-Cancer Drugs

Fumitremorgins and Relatives – From Tremorgenic Compounds to Valuable Anti-Cancer Drugs

Tetrahydroquinoline/4,5‐Dihydroisoxazole Molecular Hybrids as Inhibitors of Breast Cancer Resistance Protein (BCRP/ABCG2)

Synthesis, Density Functional Theory Band Structure Calculations, Optical, and Photoelectrical Characterizations of the Novel (9‐Bromo‐3‐cyano‐5‐oxo‐1,5‐dihydro‐2H‐chromeno[4,3‐b]pyridin‐2‐ylidene)propanedinitrile

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