1,4-naphthoquinone cations as antiplasmodial agents: Hydroxy-, acyloxy-, and alkoxy-substituted analogues

Xiao Lu; Ali Altharawi; Jiri Gut; Philip J. Rosenthal; Timothy E. Long

doi:10.1021/ml300242v

1,4-naphthoquinone cations as antiplasmodial agents: Hydroxy-, acyloxy-, and alkoxy-substituted analogues

Xiao Lu
, Ali Altharawi
, Jiri Gut
, Philip J. Rosenthal
, Timothy E. Long

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

36 Scopus citations

Abstract

Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues were found to be inactive as antagonists of parasite growth, which was attributed to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent, the antiplasmodial activity was restored in the sub-100 nM range. Optimal inhibitors were found to possess IC₅₀ values of 17.4-49.5 nM against heteroresistant P. falciparum W2.

Original language	English
Pages (from-to)	1029-1033
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	12
DOIs	https://doi.org/10.1021/ml300242v
State	Published - 13 Dec 2012
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

1,4-naphthoquinones
Plasmodium
malaria
phosphonium cations

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10.1021/ml300242v

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title = "1,4-naphthoquinone cations as antiplasmodial agents: Hydroxy-, acyloxy-, and alkoxy-substituted analogues",

abstract = "Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues were found to be inactive as antagonists of parasite growth, which was attributed to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent, the antiplasmodial activity was restored in the sub-100 nM range. Optimal inhibitors were found to possess IC50 values of 17.4-49.5 nM against heteroresistant P. falciparum W2.",

keywords = "1,4-naphthoquinones, Plasmodium, malaria, phosphonium cations",

author = "Xiao Lu and Ali Altharawi and Jiri Gut and Rosenthal, \{Philip J.\} and Long, \{Timothy E.\}",

year = "2012",

month = dec,

day = "13",

doi = "10.1021/ml300242v",

language = "English",

volume = "3",

pages = "1029--1033",

journal = "ACS Medicinal Chemistry Letters",

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TY - JOUR

T1 - 1,4-naphthoquinone cations as antiplasmodial agents

T2 - Hydroxy-, acyloxy-, and alkoxy-substituted analogues

AU - Lu, Xiao

AU - Altharawi, Ali

AU - Gut, Jiri

AU - Rosenthal, Philip J.

AU - Long, Timothy E.

PY - 2012/12/13

Y1 - 2012/12/13

N2 - Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues were found to be inactive as antagonists of parasite growth, which was attributed to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent, the antiplasmodial activity was restored in the sub-100 nM range. Optimal inhibitors were found to possess IC50 values of 17.4-49.5 nM against heteroresistant P. falciparum W2.

AB - Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues were found to be inactive as antagonists of parasite growth, which was attributed to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent, the antiplasmodial activity was restored in the sub-100 nM range. Optimal inhibitors were found to possess IC50 values of 17.4-49.5 nM against heteroresistant P. falciparum W2.

KW - 1,4-naphthoquinones

KW - Plasmodium

KW - malaria

KW - phosphonium cations

UR - https://www.scopus.com/pages/publications/84871226257

U2 - 10.1021/ml300242v

DO - 10.1021/ml300242v

M3 - Article

AN - SCOPUS:84871226257

SN - 1948-5875

VL - 3

SP - 1029

EP - 1033

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 12

ER -

1,4-naphthoquinone cations as antiplasmodial agents: Hydroxy-, acyloxy-, and alkoxy-substituted analogues

Abstract

UN SDGs

Keywords

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