Optimizing the flavanone core toward new selective nitrogen-containing modulators of ABC transporters

Ricardo J. Ferreira; Rafael Baptista; Alexis Moreno; Patricia G Madeira; Ruttiros Khonkarn; Hélène Baubichon-Cortay; Daniel Jva Dos Santos; Pierre Falson; Maria-José U Ferreira

doi:10.4155/fmc-2017-0228

Optimizing the flavanone core toward new selective nitrogen-containing modulators of ABC transporters

Ricardo J. Ferreira, Rafael Baptista, Alexis Moreno, Patricia G Madeira, Ruttiros Khonkarn, Hélène Baubichon-Cortay, Daniel Jva Dos Santos, Pierre Falson, Maria-José U Ferreira

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Abstract

AIM: Naringenin (1), isolated in large amount from the aerial parts of Euphorbia pedroi, was chemically derivatized to yield 18 imine derivatives (2-19) and three alkylated derivatives through a Mannich-type reaction (20-22) that were tested as multidrug resistance (MDR) reversers in cancer cells. Results/methodology: While hydrazone (2-4) and azine (5-13) derivatives showed an improvement in their MDR reversal activities against the breast cancer resistance protein, carbohydrazides 14-19 revealed an enhancement in MDR reversal activity toward the multidrug resistance protein 1.

CONCLUSION: The observed activities, together with pharmacophoric analysis and molecular docking studies, identified the spatial orientation of the substituents as a key structural feature toward a possible mechanism by which naringenin derivatives may reverse MDR in cancer.

Original language	English
Journal	Future Medicinal Chemistry
Volume	10
Issue number	7
Early online date	23 Mar 2018
DOIs	https://doi.org/10.4155/fmc-2017-0228
Publication status	Published - 01 Apr 2018
Externally published	Yes

Keywords

ABC transporters
BCRP
flavanone
hydrazides
hydrazones
molecular docking
MRP1
multidrug resistance
P-gp
pharmacophore

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Optimizing the flavanone core towards new selective nitrogen-containing modulators of ABC transportersAccepted author manuscript, 992 KB

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@article{01c64323021a4e40836d497a204cddc6,

title = "Optimizing the flavanone core toward new selective nitrogen-containing modulators of ABC transporters",

abstract = "AIM: Naringenin (1), isolated in large amount from the aerial parts of Euphorbia pedroi, was chemically derivatized to yield 18 imine derivatives (2-19) and three alkylated derivatives through a Mannich-type reaction (20-22) that were tested as multidrug resistance (MDR) reversers in cancer cells. Results/methodology: While hydrazone (2-4) and azine (5-13) derivatives showed an improvement in their MDR reversal activities against the breast cancer resistance protein, carbohydrazides 14-19 revealed an enhancement in MDR reversal activity toward the multidrug resistance protein 1.CONCLUSION: The observed activities, together with pharmacophoric analysis and molecular docking studies, identified the spatial orientation of the substituents as a key structural feature toward a possible mechanism by which naringenin derivatives may reverse MDR in cancer.",

keywords = "ABC transporters, BCRP, flavanone, hydrazides, hydrazones, molecular docking, MRP1, multidrug resistance, P-gp, pharmacophore",

author = "Ferreira, {Ricardo J.} and Rafael Baptista and Alexis Moreno and Madeira, {Patricia G} and Ruttiros Khonkarn and H{\'e}l{\`e}ne Baubichon-Cortay and {Dos Santos}, {Daniel Jva} and Pierre Falson and Ferreira, {Maria-Jos{\'e} U}",

year = "2018",

month = apr,

day = "1",

doi = "10.4155/fmc-2017-0228",

language = "English",

volume = "10",

journal = "Future Medicinal Chemistry",

issn = "1756-8919",

publisher = "Taylor & Francis",

number = "7",

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TY - JOUR

T1 - Optimizing the flavanone core toward new selective nitrogen-containing modulators of ABC transporters

AU - Ferreira, Ricardo J.

AU - Baptista, Rafael

AU - Moreno, Alexis

AU - Madeira, Patricia G

AU - Khonkarn, Ruttiros

AU - Baubichon-Cortay, Hélène

AU - Dos Santos, Daniel Jva

AU - Falson, Pierre

AU - Ferreira, Maria-José U

PY - 2018/4/1

Y1 - 2018/4/1

N2 - AIM: Naringenin (1), isolated in large amount from the aerial parts of Euphorbia pedroi, was chemically derivatized to yield 18 imine derivatives (2-19) and three alkylated derivatives through a Mannich-type reaction (20-22) that were tested as multidrug resistance (MDR) reversers in cancer cells. Results/methodology: While hydrazone (2-4) and azine (5-13) derivatives showed an improvement in their MDR reversal activities against the breast cancer resistance protein, carbohydrazides 14-19 revealed an enhancement in MDR reversal activity toward the multidrug resistance protein 1.CONCLUSION: The observed activities, together with pharmacophoric analysis and molecular docking studies, identified the spatial orientation of the substituents as a key structural feature toward a possible mechanism by which naringenin derivatives may reverse MDR in cancer.

AB - AIM: Naringenin (1), isolated in large amount from the aerial parts of Euphorbia pedroi, was chemically derivatized to yield 18 imine derivatives (2-19) and three alkylated derivatives through a Mannich-type reaction (20-22) that were tested as multidrug resistance (MDR) reversers in cancer cells. Results/methodology: While hydrazone (2-4) and azine (5-13) derivatives showed an improvement in their MDR reversal activities against the breast cancer resistance protein, carbohydrazides 14-19 revealed an enhancement in MDR reversal activity toward the multidrug resistance protein 1.CONCLUSION: The observed activities, together with pharmacophoric analysis and molecular docking studies, identified the spatial orientation of the substituents as a key structural feature toward a possible mechanism by which naringenin derivatives may reverse MDR in cancer.

KW - ABC transporters

KW - BCRP

KW - flavanone

KW - hydrazides

KW - hydrazones

KW - molecular docking

KW - MRP1

KW - multidrug resistance

KW - P-gp

KW - pharmacophore

U2 - 10.4155/fmc-2017-0228

DO - 10.4155/fmc-2017-0228

M3 - Article

C2 - 29570361

SN - 1756-8919

VL - 10

JO - Future Medicinal Chemistry

JF - Future Medicinal Chemistry

IS - 7

ER -

Optimizing the flavanone core toward new selective nitrogen-containing modulators of ABC transporters

Abstract

Keywords

UN SDGs

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