Novel Coumarin-Quinoline Hybrids: Design of Multitarget Compounds for Alzheimer's Disease

Yorley Duarte, André Fonseca, Margarita Gutiérrez, Francisco Adasme-Carreño, Camila Muñoz-Gutierrez, Jans Alzate-Morales, Lourdes Santana, Eugenio Uriarte, Rocío Álvarez, Maria João Matos

Resultado de la investigación: Article

5 Citas (Scopus)

Resumen

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, presenting the most devastating consequences on human health and life quality. Coumarin-quinoline hybrids were synthesized following a very efficient and versatile strategy. Small structural variations contributed to dual acetyl/butyrylcholinesterases (AChE/BuChE) activity or selectivity towards one of these enzymes. In addition, some of the studied compounds are interesting iron chelators, presenting a tendency to be neuroprotective. Moreover, the compounds are not cytotoxic for SH-SY5Y neuroblastoma cells. Compound 9c proved to be the most interesting compound of the studied series. This compound is selective against AChE and proved to be an excellent iron chelating agent (iron chelation at 100 μM=72.87%). Molecular docking studies were performed to establish the nature of the interaction between the studied compounds and the binding pockets, leading to a rationalization of structure–activity relationships. Compound 9c forms a well-defined π-stacking interaction with Phe330 and interacts with Tyr121 residue via a hydrogen bond, while the inactive compounds cannot establish these interactions. Important preliminary results against different targets, as well as some structure–activity relationships, were concluded from the experimental results.

Idioma originalEnglish
Páginas (desde-hasta)551-558
Número de páginas8
PublicaciónChemistrySelect
Volumen4
N.º2
DOI
EstadoPublished - 17 ene 2019

Huella dactilar

Iron
Iron Chelating Agents
Neurodegenerative diseases
Butyrylcholinesterase
Chelating Agents
Chelation
Hydrogen bonds
Health
Enzymes
coumarin
quinoline

ASJC Scopus subject areas

  • Chemistry(all)

Citar esto

Duarte, Y., Fonseca, A., Gutiérrez, M., Adasme-Carreño, F., Muñoz-Gutierrez, C., Alzate-Morales, J., ... Matos, M. J. (2019). Novel Coumarin-Quinoline Hybrids: Design of Multitarget Compounds for Alzheimer's Disease. ChemistrySelect, 4(2), 551-558. https://doi.org/10.1002/slct.201803222
Duarte, Yorley ; Fonseca, André ; Gutiérrez, Margarita ; Adasme-Carreño, Francisco ; Muñoz-Gutierrez, Camila ; Alzate-Morales, Jans ; Santana, Lourdes ; Uriarte, Eugenio ; Álvarez, Rocío ; Matos, Maria João. / Novel Coumarin-Quinoline Hybrids : Design of Multitarget Compounds for Alzheimer's Disease. En: ChemistrySelect. 2019 ; Vol. 4, N.º 2. pp. 551-558.
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abstract = "Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, presenting the most devastating consequences on human health and life quality. Coumarin-quinoline hybrids were synthesized following a very efficient and versatile strategy. Small structural variations contributed to dual acetyl/butyrylcholinesterases (AChE/BuChE) activity or selectivity towards one of these enzymes. In addition, some of the studied compounds are interesting iron chelators, presenting a tendency to be neuroprotective. Moreover, the compounds are not cytotoxic for SH-SY5Y neuroblastoma cells. Compound 9c proved to be the most interesting compound of the studied series. This compound is selective against AChE and proved to be an excellent iron chelating agent (iron chelation at 100 μM=72.87{\%}). Molecular docking studies were performed to establish the nature of the interaction between the studied compounds and the binding pockets, leading to a rationalization of structure–activity relationships. Compound 9c forms a well-defined π-stacking interaction with Phe330 and interacts with Tyr121 residue via a hydrogen bond, while the inactive compounds cannot establish these interactions. Important preliminary results against different targets, as well as some structure–activity relationships, were concluded from the experimental results.",
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Duarte, Y, Fonseca, A, Gutiérrez, M, Adasme-Carreño, F, Muñoz-Gutierrez, C, Alzate-Morales, J, Santana, L, Uriarte, E, Álvarez, R & Matos, MJ 2019, 'Novel Coumarin-Quinoline Hybrids: Design of Multitarget Compounds for Alzheimer's Disease', ChemistrySelect, vol. 4, n.º 2, pp. 551-558. https://doi.org/10.1002/slct.201803222

Novel Coumarin-Quinoline Hybrids : Design of Multitarget Compounds for Alzheimer's Disease. / Duarte, Yorley; Fonseca, André; Gutiérrez, Margarita; Adasme-Carreño, Francisco; Muñoz-Gutierrez, Camila; Alzate-Morales, Jans; Santana, Lourdes; Uriarte, Eugenio; Álvarez, Rocío; Matos, Maria João.

En: ChemistrySelect, Vol. 4, N.º 2, 17.01.2019, p. 551-558.

Resultado de la investigación: Article

TY - JOUR

T1 - Novel Coumarin-Quinoline Hybrids

T2 - Design of Multitarget Compounds for Alzheimer's Disease

AU - Duarte, Yorley

AU - Fonseca, André

AU - Gutiérrez, Margarita

AU - Adasme-Carreño, Francisco

AU - Muñoz-Gutierrez, Camila

AU - Alzate-Morales, Jans

AU - Santana, Lourdes

AU - Uriarte, Eugenio

AU - Álvarez, Rocío

AU - Matos, Maria João

PY - 2019/1/17

Y1 - 2019/1/17

N2 - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, presenting the most devastating consequences on human health and life quality. Coumarin-quinoline hybrids were synthesized following a very efficient and versatile strategy. Small structural variations contributed to dual acetyl/butyrylcholinesterases (AChE/BuChE) activity or selectivity towards one of these enzymes. In addition, some of the studied compounds are interesting iron chelators, presenting a tendency to be neuroprotective. Moreover, the compounds are not cytotoxic for SH-SY5Y neuroblastoma cells. Compound 9c proved to be the most interesting compound of the studied series. This compound is selective against AChE and proved to be an excellent iron chelating agent (iron chelation at 100 μM=72.87%). Molecular docking studies were performed to establish the nature of the interaction between the studied compounds and the binding pockets, leading to a rationalization of structure–activity relationships. Compound 9c forms a well-defined π-stacking interaction with Phe330 and interacts with Tyr121 residue via a hydrogen bond, while the inactive compounds cannot establish these interactions. Important preliminary results against different targets, as well as some structure–activity relationships, were concluded from the experimental results.

AB - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, presenting the most devastating consequences on human health and life quality. Coumarin-quinoline hybrids were synthesized following a very efficient and versatile strategy. Small structural variations contributed to dual acetyl/butyrylcholinesterases (AChE/BuChE) activity or selectivity towards one of these enzymes. In addition, some of the studied compounds are interesting iron chelators, presenting a tendency to be neuroprotective. Moreover, the compounds are not cytotoxic for SH-SY5Y neuroblastoma cells. Compound 9c proved to be the most interesting compound of the studied series. This compound is selective against AChE and proved to be an excellent iron chelating agent (iron chelation at 100 μM=72.87%). Molecular docking studies were performed to establish the nature of the interaction between the studied compounds and the binding pockets, leading to a rationalization of structure–activity relationships. Compound 9c forms a well-defined π-stacking interaction with Phe330 and interacts with Tyr121 residue via a hydrogen bond, while the inactive compounds cannot establish these interactions. Important preliminary results against different targets, as well as some structure–activity relationships, were concluded from the experimental results.

KW - Acetyl/butyrylcholinesterases’ inhibitors

KW - Coumarin-quinoline hybrids

KW - Drug design

KW - Iron chelating agents

KW - Neuroprotective agents.

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U2 - 10.1002/slct.201803222

DO - 10.1002/slct.201803222

M3 - Article

AN - SCOPUS:85060222461

VL - 4

SP - 551

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JO - ChemistrySelect

JF - ChemistrySelect

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Duarte Y, Fonseca A, Gutiérrez M, Adasme-Carreño F, Muñoz-Gutierrez C, Alzate-Morales J y otros. Novel Coumarin-Quinoline Hybrids: Design of Multitarget Compounds for Alzheimer's Disease. ChemistrySelect. 2019 ene 17;4(2):551-558. https://doi.org/10.1002/slct.201803222