Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives

Scott Eagon; Jared T. Hammill; Kasey Fitzsimmons; Natalie Sienko; Brandon Nguyen; Jarvis Law; Aashrita Manjunath; Steven P. Wilkinson; Kara Thompson; Julia Elizabeth Glidden; Amy L. Rice; Mofolusho O. Falade; Joshua J. Kimball; Celine DiBernardo; R. Kiplin Guy

doi:10.1016/j.bmcl.2021.128216

Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives

Scott Eagon, Jared T. Hammill, Kasey Fitzsimmons, Natalie Sienko, Brandon Nguyen, Jarvis Law, Aashrita Manjunath, Steven P. Wilkinson, Kara Thompson, Julia Elizabeth Glidden, Amy L. Rice, Mofolusho O. Falade, Joshua J. Kimball, Celine DiBernardo, R. Kiplin Guy

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

3 Scopus citations

Abstract

Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.

Original language	English
Article number	128216
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	47
DOIs	https://doi.org/10.1016/j.bmcl.2021.128216
State	Published - Sep 1 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s)

Keywords

2,6-Dibenzylidenecyclohexanone
Malaria
Michael system
Plasmodium falciparum
Structure activity relationship

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

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

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10.1016/j.bmcl.2021.128216

Cite this

Eagon, S., Hammill, J. T., Fitzsimmons, K., Sienko, N., Nguyen, B., Law, J., Manjunath, A., Wilkinson, S. P., Thompson, K., Glidden, J. E., Rice, A. L., Falade, M. O., Kimball, J. J., DiBernardo, C., & Guy, R. K. (2021). Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives. Bioorganic and Medicinal Chemistry Letters, 47, Article 128216. https://doi.org/10.1016/j.bmcl.2021.128216

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abstract = "Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.",

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doi = "10.1016/j.bmcl.2021.128216",

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T1 - Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives

AU - Eagon, Scott

AU - Hammill, Jared T.

AU - Fitzsimmons, Kasey

AU - Sienko, Natalie

AU - Nguyen, Brandon

AU - Law, Jarvis

AU - Manjunath, Aashrita

AU - Wilkinson, Steven P.

AU - Thompson, Kara

AU - Glidden, Julia Elizabeth

AU - Rice, Amy L.

AU - Falade, Mofolusho O.

AU - Kimball, Joshua J.

AU - DiBernardo, Celine

AU - Guy, R. Kiplin

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.

AB - Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.

KW - 2,6-Dibenzylidenecyclohexanone

KW - Malaria

KW - Michael system

KW - Plasmodium falciparum

KW - Structure activity relationship

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Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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