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Plasmodium c-GMP dependent protein kinase inhibitors

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TitleInfo
Title
Plasmodium c-GMP dependent protein kinase inhibitors
Name (type = personal)
NamePart (type = family)
Fondekar
NamePart (type = given)
Raheel
NamePart (type = date)
1993-
DisplayForm
Raheel Fondekar
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Augeri
NamePart (type = given)
David J.
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David J. Augeri
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Advisory Committee
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chair
Name (type = personal)
NamePart (type = family)
Lavoie
NamePart (type = given)
Edmond
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Edmond Lavoie
Affiliation
Advisory Committee
Role
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internal member
Name (type = personal)
NamePart (type = family)
Hu
NamePart (type = given)
Lonqin
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Lonqin Hu
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
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theses
OriginInfo
DateCreated (encoding = w3cdtf); (keyDate = yes); (qualifier = exact)
2019
DateOther (encoding = w3cdtf); (qualifier = exact); (type = degree)
2019-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2019
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract (type = abstract)
Malaria is an infectious parasitic disease affecting vertebrates such as birds and animals including humans. It is caused by unicellular eukaryotes belonging to the genus Plasmodium and is transmitted by the bite of the female Anopheles mosquitoes. Plasmodium are obligate parasites which means they require a vertebrate host and the insect vector to complete their lifecycle. According to one estimate, malaria may have claimed the lives of approximately half the people to have ever walked the face of the earth. The disease-causing Plasmodium species have been around for more than a million years. Malaria asserts a deep and harrowing socio-economic effect on malaria-endemic countries. This can be inferred from the fact that most of the malaria-endemic countries are under-developed. Hence, malaria is regarded as the world’s most devastating parasitic infection. The disease is endemic to countries close to the equator as the pathogen and the insect vector thrive particularly well in tropical climates. Five species of Plasmodium are known to infect humans – P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi. Together, P. falciparum and P. vivax account for more than 90% of the human infections. The sporozoites of the parasite, introduced into the host body by the bite of the vector, find their way to the liver where they infect hepatocytes. They undergo multiplication and growth and exit hepatocytes as merozoites. Subsequently, the merozoites begin invading erythrocytes where they feast on the haemoglobin. After undergoing multiplication, the merozoites exit erythrocytes thus causing rupture and destruction of these cells. This phenomenon is attributed to high fever and chills associated with malaria patients.
Malaria eradication relies heavily on pathogen and vector control. Vector control essentially aims to prevent spread of the disease by eliminating Anopheles mosquitoes. Pathogen control, on the other hand, is essential for disease treatment and prophylaxis. It is typically accomplished with the use of antimalarial drugs. The most effective antimalarial drug therapy as of today is artemisinin combination therapies (ACTs). However, with the recent rise in artemisinin resistance reported in several countries in Southeast Asia, the urgency to develop new antimalarial drugs is rapidly increasing. In addition, the parasites have long-developed resistance to most of the existing antimalarials like chloroquine, quinine and mefloquine which makes the fight against malaria even more grave.
Plasmodium c-GMP dependent protein kinase (PKG) has been extensively researched in recent times as a potential means of pathogen control. The enzyme has been found to have a crucial role in each of the lifecycle stages of the parasite. Studies have shown that parasitic invasion of the hepatocytes, growth related schizogony in the erythrocytes and gametogenesis occurring in the mosquito cycle can all be linked to Plasmodium PKG. This makes parasitic PKG a very attractive target not only for malaria treatment, but also for prophylaxis. Trisubstituted pyrrole (TSP) has been identified as a potent and selective inhibitor of parasitic PKG. As a result, PKG inhibitors were synthesized to optimize the activity and selectivity of TSP and to generate a much-needed SAR in order to map the floor of the binding pocket of the enzyme. The optimization process involved introduction of a wide range of substituents at different locations of the TSP structure. A few new scaffolds were also investigated to evaluate activity and further SAR knowledge. In the biological assay performed, TSP (18 nM) and several potent analogues were identified.
Subject (authority = RUETD)
Topic
Medicinal Chemistry
Subject (authority = LCSH)
Topic
Plasmodium -- Genetic aspects
Subject (authority = LCSH)
Topic
Malaria -- Prevention
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_10062
PhysicalDescription
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application/pdf
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text/xml
Extent
1 online resource (xii, 122 pages) : illustrations
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
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TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-cfn1-kn52
Genre (authority = ExL-Esploro)
ETD graduate
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Fondekar
GivenName
Raheel
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-05-22 12:56:03
AssociatedEntity
Name
Raheel Fondekar
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

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ETD
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windows xp
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1.7
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2019-07-03T14:59:09
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2019-07-03T14:59:09
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