Synthesis and structure-activity relationships of antimalarial 4-oxo-3-carboxyl quinolones

Yiqun Zhang; W. Armand Guiguemde; Martina Sigal; Fangyi Zhu; Michele C. Connelly; Solomon Nwaka; R. Kiplin Guy

doi:10.1016/j.bmc.2010.02.013

Synthesis and structure-activity relationships of antimalarial 4-oxo-3-carboxyl quinolones

Yiqun Zhang, W. Armand Guiguemde, Martina Sigal, Fangyi Zhu, Michele C. Connelly, Solomon Nwaka, R. Kiplin Guy

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

40 Scopus citations

Abstract

Malaria is endemic in tropical and subtropical regions of Africa, Asia, and the Americas. The increasing prevalence of multi-drug-resistant Plasmodium falciparum drives the ongoing need for the development of new antimalarial drugs. In this light, novel scaffolds to which the parasite has not been exposed are of particular interest. Recently, workers at the Swiss Tropical Institute discovered two novel 4-oxo-3-carboxyl quinolones active against the intra-erythrocytic stages of P. falciparum while carrying out rationally directed low-throughput screening of potential antimalarial agents as part of an effort directed by the World Health Organization. Here we report the design, synthesis, and preliminary pharmacologic characterization of a series of analogues of 4-oxo-3-carboxyl quinolones. These studies indicate that the series has good potential for preclinical development.

Original language	English
Pages (from-to)	2756-2766
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	7
DOIs	https://doi.org/10.1016/j.bmc.2010.02.013
State	Published - Apr 1 2010

Bibliographical note

Funding Information:
We thank Jean-Marc Paris and Allan Reitz for helpful discussions during the course of these studies. This work was funded by World Health Organization Grant 180738010 , the American Lebanese Syrian Associated Charities (ALSAC) , and St. Jude Children’s Research Hospital .

Keywords

Malaria
Plasmodium
Quinolones
Synthesis

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)

Access to Document

10.1016/j.bmc.2010.02.013

Cite this

@article{79df902e515243c7abed38bb6ab98621,

title = "Synthesis and structure-activity relationships of antimalarial 4-oxo-3-carboxyl quinolones",

abstract = "Malaria is endemic in tropical and subtropical regions of Africa, Asia, and the Americas. The increasing prevalence of multi-drug-resistant Plasmodium falciparum drives the ongoing need for the development of new antimalarial drugs. In this light, novel scaffolds to which the parasite has not been exposed are of particular interest. Recently, workers at the Swiss Tropical Institute discovered two novel 4-oxo-3-carboxyl quinolones active against the intra-erythrocytic stages of P. falciparum while carrying out rationally directed low-throughput screening of potential antimalarial agents as part of an effort directed by the World Health Organization. Here we report the design, synthesis, and preliminary pharmacologic characterization of a series of analogues of 4-oxo-3-carboxyl quinolones. These studies indicate that the series has good potential for preclinical development.",

keywords = "Malaria, Plasmodium, Quinolones, Synthesis",

author = "Yiqun Zhang and Guiguemde, {W. Armand} and Martina Sigal and Fangyi Zhu and Connelly, {Michele C.} and Solomon Nwaka and Guy, {R. Kiplin}",

note = "Funding Information: We thank Jean-Marc Paris and Allan Reitz for helpful discussions during the course of these studies. This work was funded by World Health Organization Grant 180738010 , the American Lebanese Syrian Associated Charities (ALSAC) , and St. Jude Children{\textquoteright}s Research Hospital . ",

year = "2010",

month = apr,

day = "1",

doi = "10.1016/j.bmc.2010.02.013",

language = "English",

volume = "18",

pages = "2756--2766",

number = "7",

}

TY - JOUR

T1 - Synthesis and structure-activity relationships of antimalarial 4-oxo-3-carboxyl quinolones

AU - Zhang, Yiqun

AU - Guiguemde, W. Armand

AU - Sigal, Martina

AU - Zhu, Fangyi

AU - Connelly, Michele C.

AU - Nwaka, Solomon

AU - Guy, R. Kiplin

N1 - Funding Information: We thank Jean-Marc Paris and Allan Reitz for helpful discussions during the course of these studies. This work was funded by World Health Organization Grant 180738010 , the American Lebanese Syrian Associated Charities (ALSAC) , and St. Jude Children’s Research Hospital .

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Malaria is endemic in tropical and subtropical regions of Africa, Asia, and the Americas. The increasing prevalence of multi-drug-resistant Plasmodium falciparum drives the ongoing need for the development of new antimalarial drugs. In this light, novel scaffolds to which the parasite has not been exposed are of particular interest. Recently, workers at the Swiss Tropical Institute discovered two novel 4-oxo-3-carboxyl quinolones active against the intra-erythrocytic stages of P. falciparum while carrying out rationally directed low-throughput screening of potential antimalarial agents as part of an effort directed by the World Health Organization. Here we report the design, synthesis, and preliminary pharmacologic characterization of a series of analogues of 4-oxo-3-carboxyl quinolones. These studies indicate that the series has good potential for preclinical development.

AB - Malaria is endemic in tropical and subtropical regions of Africa, Asia, and the Americas. The increasing prevalence of multi-drug-resistant Plasmodium falciparum drives the ongoing need for the development of new antimalarial drugs. In this light, novel scaffolds to which the parasite has not been exposed are of particular interest. Recently, workers at the Swiss Tropical Institute discovered two novel 4-oxo-3-carboxyl quinolones active against the intra-erythrocytic stages of P. falciparum while carrying out rationally directed low-throughput screening of potential antimalarial agents as part of an effort directed by the World Health Organization. Here we report the design, synthesis, and preliminary pharmacologic characterization of a series of analogues of 4-oxo-3-carboxyl quinolones. These studies indicate that the series has good potential for preclinical development.

KW - Malaria

KW - Plasmodium

KW - Quinolones

KW - Synthesis

UR - http://www.scopus.com/inward/record.url?scp=77950031114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950031114&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2010.02.013

DO - 10.1016/j.bmc.2010.02.013

M3 - Article

C2 - 20206533

AN - SCOPUS:77950031114

SN - 0968-0896

VL - 18

SP - 2756

EP - 2766

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 7

ER -

Synthesis and structure-activity relationships of antimalarial 4-oxo-3-carboxyl quinolones

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this