3D-QSAR, design, synthesis and characterization of trisubstituted harmine derivatives with in vitro antiproliferative properties

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Apolar trisubstituted derivatives of harmine show high antiproliferative activity on diverse cancer cell lines. However, these molecules present a poor solubility making these compounds poorly bioavailable. Here, new compounds were synthesized in order to improve solubility while retaining antiproliferative activity. First, polar substituents have shown a higher solubility but a loss of antiproliferative activity. Second, a Comparative Molecular Field Analysis (CoMFA) model was developed, guiding the design and synthesis of eight new compounds. Characterization has underlined the in vitro antiproliferative character of these compounds on five cancerous cell lines, combining with a high solubility at physiological pH, making these molecules druggable. Moreover, targeting glioma treatment, human intestinal absorption and blood brain penetration have been calculated, showing high absorption and penetration properties.

langue originaleAnglais
Numéro d'article7726
Pages (de - à)45-55
Nombre de pages11
journalEuropean Journal of Medicinal Chemistry
Volume94
Les DOIs
étatPublié - 13 avr. 2015

Empreinte digitale

Harmine
Quantitative Structure-Activity Relationship
Solubility
Derivatives
Cells
Cell Line
Molecules
Intestinal Absorption
Glioma
Brain
Blood
In Vitro Techniques
Neoplasms

Citer ceci

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title = "3D-QSAR, design, synthesis and characterization of trisubstituted harmine derivatives with in vitro antiproliferative properties",
abstract = "Apolar trisubstituted derivatives of harmine show high antiproliferative activity on diverse cancer cell lines. However, these molecules present a poor solubility making these compounds poorly bioavailable. Here, new compounds were synthesized in order to improve solubility while retaining antiproliferative activity. First, polar substituents have shown a higher solubility but a loss of antiproliferative activity. Second, a Comparative Molecular Field Analysis (CoMFA) model was developed, guiding the design and synthesis of eight new compounds. Characterization has underlined the in vitro antiproliferative character of these compounds on five cancerous cell lines, combining with a high solubility at physiological pH, making these molecules druggable. Moreover, targeting glioma treatment, human intestinal absorption and blood brain penetration have been calculated, showing high absorption and penetration properties.",
keywords = "Antiproliferative activity, Comparative molecular field analysis, Cytostatic activity, Harmine derivatives",
author = "C{\'e}line Meinguet and C{\'e}line Bruy{\`e}re and Rapha{\"e}l Fr{\'e}d{\'e}rick and V{\'e}ronique Mathieu and Christelle Vancraeynest and Lionel Pochet and Julie Laloy and J{\'e}r{\'e}mie Mortier and Gerhard Wolber and Robert Kiss and Bernard Masereel and Johan Wouters",
note = "Copyright {\circledC} 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.",
year = "2015",
month = "4",
day = "13",
doi = "10.1016/j.ejmech.2015.02.044",
language = "English",
volume = "94",
pages = "45--55",
journal = "European journal of medicinal chemistry / Chimica therapeutica",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

TY - JOUR

T1 - 3D-QSAR, design, synthesis and characterization of trisubstituted harmine derivatives with in vitro antiproliferative properties

AU - Meinguet, Céline

AU - Bruyère, Céline

AU - Frédérick, Raphaël

AU - Mathieu, Véronique

AU - Vancraeynest, Christelle

AU - Pochet, Lionel

AU - Laloy, Julie

AU - Mortier, Jérémie

AU - Wolber, Gerhard

AU - Kiss, Robert

AU - Masereel, Bernard

AU - Wouters, Johan

N1 - Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

PY - 2015/4/13

Y1 - 2015/4/13

N2 - Apolar trisubstituted derivatives of harmine show high antiproliferative activity on diverse cancer cell lines. However, these molecules present a poor solubility making these compounds poorly bioavailable. Here, new compounds were synthesized in order to improve solubility while retaining antiproliferative activity. First, polar substituents have shown a higher solubility but a loss of antiproliferative activity. Second, a Comparative Molecular Field Analysis (CoMFA) model was developed, guiding the design and synthesis of eight new compounds. Characterization has underlined the in vitro antiproliferative character of these compounds on five cancerous cell lines, combining with a high solubility at physiological pH, making these molecules druggable. Moreover, targeting glioma treatment, human intestinal absorption and blood brain penetration have been calculated, showing high absorption and penetration properties.

AB - Apolar trisubstituted derivatives of harmine show high antiproliferative activity on diverse cancer cell lines. However, these molecules present a poor solubility making these compounds poorly bioavailable. Here, new compounds were synthesized in order to improve solubility while retaining antiproliferative activity. First, polar substituents have shown a higher solubility but a loss of antiproliferative activity. Second, a Comparative Molecular Field Analysis (CoMFA) model was developed, guiding the design and synthesis of eight new compounds. Characterization has underlined the in vitro antiproliferative character of these compounds on five cancerous cell lines, combining with a high solubility at physiological pH, making these molecules druggable. Moreover, targeting glioma treatment, human intestinal absorption and blood brain penetration have been calculated, showing high absorption and penetration properties.

KW - Antiproliferative activity

KW - Comparative molecular field analysis

KW - Cytostatic activity

KW - Harmine derivatives

UR - http://www.scopus.com/inward/record.url?scp=84983070540&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2015.02.044

DO - 10.1016/j.ejmech.2015.02.044

M3 - Article

VL - 94

SP - 45

EP - 55

JO - European journal of medicinal chemistry / Chimica therapeutica

JF - European journal of medicinal chemistry / Chimica therapeutica

SN - 0223-5234

M1 - 7726

ER -