Discovery of iminobenzimidazole derivatives as novel cytotoxic agents

Nora Chouha; Hassan Hammoud; Simone Brogi; Giuseppe Campiani; Caroline Welsch; Caroline Robert; Stéphan Vagner; Thierry Cresteil; Embarek Bentouhami; Laurent Désaubry

doi:10.2174/1874104501812010074

Discovery of iminobenzimidazole derivatives as novel cytotoxic agents

Nora Chouha, Hassan Hammoud, Simone Brogi, Giuseppe Campiani, Caroline Welsch, Caroline Robert, Stéphan Vagner, Thierry Cresteil, Embarek Bentouhami, Laurent Désaubry

Research output: Contribution to journal › Letter › peer-review

Abstract

In our quest to identify inhibitors of the eukaryotic translation initiation factor 4F (eIF4F), we serendipitously discovered a novel cytotoxic agent. Even though this compound did not inhibit translation, we explored the structural requirements for its cytotoxicity due to its structural originality. A series of 1,3-disubstituted iminobenzimidazoles was synthesized and evaluated for their in vitro cytotoxicity. The structure-activity relationship studies demonstrate that hydrophobic substituent is essential for activity. The most active compounds displayed a cytotoxicity in KB, HL60 and HCT116 human cancer cells with an IC₅₀ of about 1μM. These first-in-class series of low molecular weight synthetic molecules may provide the basis for the development of new anticancer drugs.

Original language	English
Pages (from-to)	74-83
Number of pages	10
Journal	Open Medicinal Chemistry Journal
Volume	12
Issue number	1
DOIs	https://doi.org/10.2174/1874104501812010074
Publication status	Published - 1 Jan 2018
Externally published	Yes

Keywords

Apoptosis
Cancer
Cytotoxicity
Eukaryotic translation initiation factor 4F
Iminobenzimidazoles
Structure-activity relationship

UN SDGs

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

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10.2174/1874104501812010074

Cite this

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title = "Discovery of iminobenzimidazole derivatives as novel cytotoxic agents",

abstract = "In our quest to identify inhibitors of the eukaryotic translation initiation factor 4F (eIF4F), we serendipitously discovered a novel cytotoxic agent. Even though this compound did not inhibit translation, we explored the structural requirements for its cytotoxicity due to its structural originality. A series of 1,3-disubstituted iminobenzimidazoles was synthesized and evaluated for their in vitro cytotoxicity. The structure-activity relationship studies demonstrate that hydrophobic substituent is essential for activity. The most active compounds displayed a cytotoxicity in KB, HL60 and HCT116 human cancer cells with an IC50 of about 1μM. These first-in-class series of low molecular weight synthetic molecules may provide the basis for the development of new anticancer drugs.",

keywords = "Apoptosis, Cancer, Cytotoxicity, Eukaryotic translation initiation factor 4F, Iminobenzimidazoles, Structure-activity relationship",

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doi = "10.2174/1874104501812010074",

language = "English",

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TY - JOUR

T1 - Discovery of iminobenzimidazole derivatives as novel cytotoxic agents

AU - Chouha, Nora

AU - Hammoud, Hassan

AU - Brogi, Simone

AU - Campiani, Giuseppe

AU - Welsch, Caroline

AU - Robert, Caroline

AU - Vagner, Stéphan

AU - Cresteil, Thierry

AU - Bentouhami, Embarek

AU - Désaubry, Laurent

PY - 2018/1/1

Y1 - 2018/1/1

N2 - In our quest to identify inhibitors of the eukaryotic translation initiation factor 4F (eIF4F), we serendipitously discovered a novel cytotoxic agent. Even though this compound did not inhibit translation, we explored the structural requirements for its cytotoxicity due to its structural originality. A series of 1,3-disubstituted iminobenzimidazoles was synthesized and evaluated for their in vitro cytotoxicity. The structure-activity relationship studies demonstrate that hydrophobic substituent is essential for activity. The most active compounds displayed a cytotoxicity in KB, HL60 and HCT116 human cancer cells with an IC50 of about 1μM. These first-in-class series of low molecular weight synthetic molecules may provide the basis for the development of new anticancer drugs.

AB - In our quest to identify inhibitors of the eukaryotic translation initiation factor 4F (eIF4F), we serendipitously discovered a novel cytotoxic agent. Even though this compound did not inhibit translation, we explored the structural requirements for its cytotoxicity due to its structural originality. A series of 1,3-disubstituted iminobenzimidazoles was synthesized and evaluated for their in vitro cytotoxicity. The structure-activity relationship studies demonstrate that hydrophobic substituent is essential for activity. The most active compounds displayed a cytotoxicity in KB, HL60 and HCT116 human cancer cells with an IC50 of about 1μM. These first-in-class series of low molecular weight synthetic molecules may provide the basis for the development of new anticancer drugs.

KW - Apoptosis

KW - Cancer

KW - Cytotoxicity

KW - Eukaryotic translation initiation factor 4F

KW - Iminobenzimidazoles

KW - Structure-activity relationship

U2 - 10.2174/1874104501812010074

DO - 10.2174/1874104501812010074

M3 - Letter

AN - SCOPUS:85053672023

SN - 1874-1045

VL - 12

SP - 74

EP - 83

JO - Open Medicinal Chemistry Journal

JF - Open Medicinal Chemistry Journal

IS - 1

ER -

Discovery of iminobenzimidazole derivatives as novel cytotoxic agents

Abstract

Keywords

UN SDGs

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