QSAR Model of Indeno[1,2-<i>b</i>]indole Derivatives and Identification of <i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a Potent CK2 Inhibitor
Casein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and <i>para</i>-quino...
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Language: | English |
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MDPI AG
2019-12-01
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Series: | Molecules |
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Online Access: | https://www.mdpi.com/1420-3049/25/1/97 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Samer Haidar Christelle Marminon Dagmar Aichele Abdelhamid Nacereddine Wael Zeinyeh Abdeslem Bouzina Malika Berredjem Laurent Ettouati Zouhair Bouaziz Marc Le Borgne Joachim Jose |
spellingShingle |
Samer Haidar Christelle Marminon Dagmar Aichele Abdelhamid Nacereddine Wael Zeinyeh Abdeslem Bouzina Malika Berredjem Laurent Ettouati Zouhair Bouaziz Marc Le Borgne Joachim Jose QSAR Model of Indeno[1,2-<i>b</i>]indole Derivatives and Identification of <i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a Potent CK2 Inhibitor Molecules qsar cancer ck2 indeno[1,2-<i>b</i>]indole naphtho[2,3-<i>b</i>]furan-4,9-dione |
author_facet |
Samer Haidar Christelle Marminon Dagmar Aichele Abdelhamid Nacereddine Wael Zeinyeh Abdeslem Bouzina Malika Berredjem Laurent Ettouati Zouhair Bouaziz Marc Le Borgne Joachim Jose |
author_sort |
Samer Haidar |
title |
QSAR Model of Indeno[1,2-<i>b</i>]indole Derivatives and Identification of <i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a Potent CK2 Inhibitor |
title_short |
QSAR Model of Indeno[1,2-<i>b</i>]indole Derivatives and Identification of <i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a Potent CK2 Inhibitor |
title_full |
QSAR Model of Indeno[1,2-<i>b</i>]indole Derivatives and Identification of <i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a Potent CK2 Inhibitor |
title_fullStr |
QSAR Model of Indeno[1,2-<i>b</i>]indole Derivatives and Identification of <i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a Potent CK2 Inhibitor |
title_full_unstemmed |
QSAR Model of Indeno[1,2-<i>b</i>]indole Derivatives and Identification of <i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a Potent CK2 Inhibitor |
title_sort |
qsar model of indeno[1,2-<i>b</i>]indole derivatives and identification of <i>n</i>-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a potent ck2 inhibitor |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2019-12-01 |
description |
Casein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and <i>para</i>-quinonic indeno[1,2-<i>b</i>]indole derivatives as CK2 inhibitors. The most active compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-<i>b</i>]indole-9,10-dione <b>4h</b> and 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-<i>b</i>]indole-9,10-dione <b>4w</b> with identical IC<sub>50</sub> values of 0.11 µM. Furthermore, the development of a QSAR model based on the structure of indeno[1,2-<i>b</i>]indoles was performed. This model was used to predict the activity of 25 compounds with naphtho[2,3-<i>b</i>]furan-4,9-dione derivatives, which were previously predicted as CK2 inhibitors via a molecular modeling approach. The activities of four naphtho[2,3-<i>b</i>]furan-4,9-dione derivatives were determined in vitro and one of them (<i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide) turned out to inhibit CK2 with an IC<sub>50</sub> value of 2.33 µM. All four candidates were able to reduce the cell viability by more than 60% after 24 h of incubation using 10 µM. |
topic |
qsar cancer ck2 indeno[1,2-<i>b</i>]indole naphtho[2,3-<i>b</i>]furan-4,9-dione |
url |
https://www.mdpi.com/1420-3049/25/1/97 |
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doaj-cead735122584236b050184220a83eb42020-11-25T02:19:36ZengMDPI AGMolecules1420-30492019-12-012519710.3390/molecules25010097molecules25010097QSAR Model of Indeno[1,2-<i>b</i>]indole Derivatives and Identification of <i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide as a Potent CK2 InhibitorSamer Haidar0Christelle Marminon1Dagmar Aichele2Abdelhamid Nacereddine3Wael Zeinyeh4Abdeslem Bouzina5Malika Berredjem6Laurent Ettouati7Zouhair Bouaziz8Marc Le Borgne9Joachim Jose10Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, GermanyFaculté de Pharmacie—ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453—INSERM US7, Université de Lyon, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon CEDEX 8, FranceInstitut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, GermanyFaculté de Pharmacie—ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453—INSERM US7, Université de Lyon, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon CEDEX 8, FranceFaculté de Pharmacie—ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453—INSERM US7, Université de Lyon, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon CEDEX 8, FranceFaculté de Pharmacie—ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453—INSERM US7, Université de Lyon, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon CEDEX 8, FranceLaboratory of Applied Organic Chemistry, Synthesis of Biomolecules and Molecular Modelling Group, Badji-Mokhtar—Annaba University, Box 12, Annaba 23000, AlgeriaFaculté de Pharmacie—ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453—INSERM US7, Université de Lyon, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon CEDEX 8, FranceFaculté de Pharmacie—ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453—INSERM US7, Université de Lyon, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon CEDEX 8, FranceFaculté de Pharmacie—ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453—INSERM US7, Université de Lyon, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon CEDEX 8, FranceInstitut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, GermanyCasein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and <i>para</i>-quinonic indeno[1,2-<i>b</i>]indole derivatives as CK2 inhibitors. The most active compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-<i>b</i>]indole-9,10-dione <b>4h</b> and 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-<i>b</i>]indole-9,10-dione <b>4w</b> with identical IC<sub>50</sub> values of 0.11 µM. Furthermore, the development of a QSAR model based on the structure of indeno[1,2-<i>b</i>]indoles was performed. This model was used to predict the activity of 25 compounds with naphtho[2,3-<i>b</i>]furan-4,9-dione derivatives, which were previously predicted as CK2 inhibitors via a molecular modeling approach. The activities of four naphtho[2,3-<i>b</i>]furan-4,9-dione derivatives were determined in vitro and one of them (<i>N</i>-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-<i>b</i>]furan-3-carboxamide) turned out to inhibit CK2 with an IC<sub>50</sub> value of 2.33 µM. All four candidates were able to reduce the cell viability by more than 60% after 24 h of incubation using 10 µM.https://www.mdpi.com/1420-3049/25/1/97qsarcancerck2indeno[1,2-<i>b</i>]indolenaphtho[2,3-<i>b</i>]furan-4,9-dione |