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)

Funding

This work was supported by the Bill and Linda Frost Fund at California Polytechnic State University (no associated grant number).

Funders
Bill and Linda Frost Fund
California State Polytechnic University Pomona

UN SDGs

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

SDG 3 Good Health and Well-being

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

Access to Document

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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title = "Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives",

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",

language = "English",

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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

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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

UR - https://www.scopus.com/pages/publications/85108955110

UR - https://www.scopus.com/pages/publications/85108955110#tab=citedBy

U2 - 10.1016/j.bmcl.2021.128216

DO - 10.1016/j.bmcl.2021.128216

M3 - Article

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AN - SCOPUS:85108955110

SN - 0960-894X

VL - 47

JO - Bioorganic and Medicinal Chemistry Letters

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M1 - 128216

ER -

Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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