Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials

[Image: see text] In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of on...

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Autores principales: Murugesan, Dinakaran, Mital, Alka, Kaiser, Marcel, Shackleford, David M., Morizzi, Julia, Katneni, Kasiram, Campbell, Michael, Hudson, Alan, Charman, Susan A., Yeates, Clive, Gilbert, Ian H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2013
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624797/
https://www.ncbi.nlm.nih.gov/pubmed/23517371
http://dx.doi.org/10.1021/jm400009c
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author Murugesan, Dinakaran
Mital, Alka
Kaiser, Marcel
Shackleford, David M.
Morizzi, Julia
Katneni, Kasiram
Campbell, Michael
Hudson, Alan
Charman, Susan A.
Yeates, Clive
Gilbert, Ian H.
author_facet Murugesan, Dinakaran
Mital, Alka
Kaiser, Marcel
Shackleford, David M.
Morizzi, Julia
Katneni, Kasiram
Campbell, Michael
Hudson, Alan
Charman, Susan A.
Yeates, Clive
Gilbert, Ian H.
author_sort Murugesan, Dinakaran
collection PubMed
description [Image: see text] In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC(50) ∼ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure–activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
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spelling pubmed-36247972013-04-15 Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials Murugesan, Dinakaran Mital, Alka Kaiser, Marcel Shackleford, David M. Morizzi, Julia Katneni, Kasiram Campbell, Michael Hudson, Alan Charman, Susan A. Yeates, Clive Gilbert, Ian H. J Med Chem [Image: see text] In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC(50) ∼ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure–activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial. American Chemical Society 2013-03-21 2013-04-11 /pmc/articles/PMC3624797/ /pubmed/23517371 http://dx.doi.org/10.1021/jm400009c Text en Copyright © 2013 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Murugesan, Dinakaran
Mital, Alka
Kaiser, Marcel
Shackleford, David M.
Morizzi, Julia
Katneni, Kasiram
Campbell, Michael
Hudson, Alan
Charman, Susan A.
Yeates, Clive
Gilbert, Ian H.
Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials
title Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials
title_full Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials
title_fullStr Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials
title_full_unstemmed Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials
title_short Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials
title_sort discovery and structure–activity relationships of pyrrolone antimalarials
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624797/
https://www.ncbi.nlm.nih.gov/pubmed/23517371
http://dx.doi.org/10.1021/jm400009c
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