Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism

Paul Schilf; Vunnam Srinivasulu; Maria L. Bolognesi; Saleh Ibrahim; Amin F. Majdalawieh; Imad A. Abu-Yousef; Hany A. Omar; Raafat ElAwady; Taleb H. Al-Tel

doi:10.1007/s00044-020-02669-3

Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism

Paul Schilf, Vunnam Srinivasulu, Maria L. Bolognesi, Saleh Ibrahim, Amin F. Majdalawieh, Imad A. Abu-Yousef, Hany A. Omar, Raafat ElAwady, Taleb H. Al-Tel^*

^*Corresponding author for this work

5 Citations (Scopus)

Abstract

Chromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse collection of chromenopyrroles. This protocol features a one-pot cascade that includes the generation of azomethine ylide and intramolecular [3 + 2]-cycloaddition. Phenotypic screening of the developed pilot library enabled the identification of chemical probes that efficiently suppress mitochondrial membrane potential, elevate reactive oxygen species content, and deplete ATP content in a hepatoma cell line (Hepa1-6), without affecting the proliferation of T- or B-cells. This selective targeting represents a new approach for the treatment of cancer. [Figure not available: see fulltext.].

Original language	English
Journal	Medicinal Chemistry Research
ISSN	1054-2523
DOIs	https://doi.org/10.1007/s00044-020-02669-3
Publication status	Published - 03.2021

Funding

This work was supported by grants from Terry Fox Foundation (grant number 120403), the Research Funding Department at the University of Sharjah (grant number 1801110125-P), and a research grant (BBRI-AS0215) to A.F.M. and I.A.A. from the American University of Sharjah.

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

SDG 3 Good Health and Well-being

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title = "Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism",

abstract = "Chromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse collection of chromenopyrroles. This protocol features a one-pot cascade that includes the generation of azomethine ylide and intramolecular [3 + 2]-cycloaddition. Phenotypic screening of the developed pilot library enabled the identification of chemical probes that efficiently suppress mitochondrial membrane potential, elevate reactive oxygen species content, and deplete ATP content in a hepatoma cell line (Hepa1-6), without affecting the proliferation of T- or B-cells. This selective targeting represents a new approach for the treatment of cancer. [Figure not available: see fulltext.].",

author = "Paul Schilf and Vunnam Srinivasulu and Bolognesi, \{Maria L.\} and Saleh Ibrahim and Majdalawieh, \{Amin F.\} and Abu-Yousef, \{Imad A.\} and Omar, \{Hany A.\} and Raafat ElAwady and Al-Tel, \{Taleb H.\}",

note = "Funding Information: This work was supported by grants from Terry Fox Foundation (grant number 120403), the Research Funding Department at the University of Sharjah (grant number 1801110125-P), and a research grant (BBRI-AS0215) to A.F.M. and I.A.A. from the American University of Sharjah. Publisher Copyright: {\textcopyright} 2020, Springer Science+Business Media, LLC, part of Springer Nature. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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doi = "10.1007/s00044-020-02669-3",

language = "English",

journal = "Medicinal Chemistry Research",

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T1 - Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism

AU - Schilf, Paul

AU - Srinivasulu, Vunnam

AU - Bolognesi, Maria L.

AU - Ibrahim, Saleh

AU - Majdalawieh, Amin F.

AU - Abu-Yousef, Imad A.

AU - Omar, Hany A.

AU - ElAwady, Raafat

AU - Al-Tel, Taleb H.

N1 - Funding Information: This work was supported by grants from Terry Fox Foundation (grant number 120403), the Research Funding Department at the University of Sharjah (grant number 1801110125-P), and a research grant (BBRI-AS0215) to A.F.M. and I.A.A. from the American University of Sharjah. Publisher Copyright: © 2020, Springer Science+Business Media, LLC, part of Springer Nature. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/3

Y1 - 2021/3

N2 - Chromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse collection of chromenopyrroles. This protocol features a one-pot cascade that includes the generation of azomethine ylide and intramolecular [3 + 2]-cycloaddition. Phenotypic screening of the developed pilot library enabled the identification of chemical probes that efficiently suppress mitochondrial membrane potential, elevate reactive oxygen species content, and deplete ATP content in a hepatoma cell line (Hepa1-6), without affecting the proliferation of T- or B-cells. This selective targeting represents a new approach for the treatment of cancer. [Figure not available: see fulltext.].

AB - Chromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse collection of chromenopyrroles. This protocol features a one-pot cascade that includes the generation of azomethine ylide and intramolecular [3 + 2]-cycloaddition. Phenotypic screening of the developed pilot library enabled the identification of chemical probes that efficiently suppress mitochondrial membrane potential, elevate reactive oxygen species content, and deplete ATP content in a hepatoma cell line (Hepa1-6), without affecting the proliferation of T- or B-cells. This selective targeting represents a new approach for the treatment of cancer. [Figure not available: see fulltext.].

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DO - 10.1007/s00044-020-02669-3

M3 - Journal articles

AN - SCOPUS:85096930827

SN - 1054-2523

JO - Medicinal Chemistry Research

JF - Medicinal Chemistry Research

ER -

Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism

Abstract

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UN SDGs

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