Discovery and optimisation studies of antimalarial phenotypic hits

Alka Mital; Dinakaran Murugesan; Marcel Kaiser; Clive Yeates; Ian H. Gilbert

doi:10.1016/j.ejmech.2015.08.044

Discovery and optimisation studies of antimalarial phenotypic hits

Alka Mital
, Dinakaran Murugesan
, Marcel Kaiser
, Clive Yeates
, Ian H. Gilbert (Lead / Corresponding author)

Biological Chemistry and Drug Discovery

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

19 Citations (Scopus)

Abstract

There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09e29 mM, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds.

Original language	English
Pages (from-to)	530-538
Number of pages	9
Journal	European Journal of Medicinal Chemistry
Volume	103
DOIs	https://doi.org/10.1016/j.ejmech.2015.08.044
Publication status	Published - 20 Oct 2015

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Malaria
Medicinal chemistry
Phenotypic hit
Plasmodium falciparum

ASJC Scopus subject areas

Drug Discovery
Organic Chemistry
Pharmacology

Access to Document

10.1016/j.ejmech.2015.08.044

Cite this

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title = "Discovery and optimisation studies of antimalarial phenotypic hits",

abstract = "There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09e29 mM, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds.",

keywords = "Malaria, Medicinal chemistry, Phenotypic hit, Plasmodium falciparum",

author = "Alka Mital and Dinakaran Murugesan and Marcel Kaiser and Clive Yeates and Gilbert, \{Ian H.\}",

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doi = "10.1016/j.ejmech.2015.08.044",

language = "English",

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journal = "European Journal of Medicinal Chemistry",

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T1 - Discovery and optimisation studies of antimalarial phenotypic hits

AU - Mital, Alka

AU - Murugesan, Dinakaran

AU - Kaiser, Marcel

AU - Yeates, Clive

AU - Gilbert, Ian H.

PY - 2015/10/20

Y1 - 2015/10/20

N2 - There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09e29 mM, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds.

AB - There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09e29 mM, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds.

KW - Malaria

KW - Medicinal chemistry

KW - Phenotypic hit

KW - Plasmodium falciparum

UR - https://www.scopus.com/pages/publications/84942595849

U2 - 10.1016/j.ejmech.2015.08.044

DO - 10.1016/j.ejmech.2015.08.044

M3 - Article

C2 - 26408453

AN - SCOPUS:84942595849

SN - 0223-5234

VL - 103

SP - 530

EP - 538

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Discovery and optimisation studies of antimalarial phenotypic hits

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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Aref#d: 19815. Wellcome Trust Centre for Drug Discovery (Strategic Award)

Cite this

Discovery and optimisation studies of antimalarial phenotypic hits

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Aref#d: 19815. Wellcome Trust Centre for Drug Discovery (Strategic Award)

Cite this