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PTA Ruthenium-aminochloroquinoline complexes: Antimalarials of the future

Silva Quintero, Maria Alejandra LU (2017) KEMR12 20162
Department of Chemistry
Abstract
Malaria is a disease that is transmitted by mosquitoes; it has been transmitedaffecting humanity for more than 10.000 years, it affects between 700 000 and 2.7million people per year and it can be deadly, therefore there is a large and increasinginterest in developing a cure against it.

Quinine, the first antimalarial, was isolated from the chinchona tree in 1632. Thiscompound was widely used in the form of tonic water, but afterwards, a decrease ofits antimalarial effectivity was observed and in 1910 it was concluded that thissituation was because the parasite that causes malaria had developed a resistanceagainst the quinine.

This situation inspired the scientific community to find new options to fight thesickness. In 1934,... (More)
Malaria is a disease that is transmitted by mosquitoes; it has been transmitedaffecting humanity for more than 10.000 years, it affects between 700 000 and 2.7million people per year and it can be deadly, therefore there is a large and increasinginterest in developing a cure against it.

Quinine, the first antimalarial, was isolated from the chinchona tree in 1632. Thiscompound was widely used in the form of tonic water, but afterwards, a decrease ofits antimalarial effectivity was observed and in 1910 it was concluded that thissituation was because the parasite that causes malaria had developed a resistanceagainst the quinine.

This situation inspired the scientific community to find new options to fight thesickness. In 1934, chloroquine was developed by German scientists and was themost used antimalarial until the 1950's, when parasitic resistance again occurred.Other medicaments like mefloquine and arteminisin have been developed but theresistance problem still exists thus maintaining interest in the development of for newtreatments.
The success of the anticancer medicine cisplatin and other metal-based drugs hasincreased interest in inorganic medicinal chemistry. Therefore scientists came to theidea of coupling a known antimalarial with a organometallic species thus creatingorganometallic antimalarial complexes that are not only effective but the parasitedoes not develop resistance against it. Studies of ferroquine, a chloroquinolinederivative coupled with a ferrocene molecule, showed fantastic results and it is inphase IIb of medical trials.

Chloroquine derivatives may be coupled with metals like ruthenium, iron, iridium andrhodium, and the first studies showed similar results (increased antimalarial activitywithout the resistance) to those from the ferroquine studies, indicating the greatfuture and potential of these compounds. This chemistry is still on in the developmentphase.

This project is involved with the development of organometallic antimalarialcompounds. Specifically ruthenium-chloroquine complexes coupled with a water-soluble phosphine molecule (PTA) were targeted in order to create antimalarialcomplexes with good aqueous solubility, which may be of importance to, theirantimalarial effectivity (Less)
Popular Abstract (Swedish)
Malaria är en sjukdom som överförs av myggor; det har överförts påverka mänskligheten i mer än 10 000 år, det påverkar mellan 700 000 och 2,7 miljoner människor per år och det kan vara dödligt, därför finns det ett stort och ökat intresse för att utveckla en bot mot den.
Quinin, den första antimalarialen, isolerades från chinchona-trädet år 1632. Denna förening användes i stor utsträckning i form av tonisk vatten, men efteråt observerade man en minskning av dess antimalarial effektivitet och år 1910 drogs slutsatsen att denna situation berodde på att parasit som orsakar malaria hade utvecklat ett motstånd mot quinin.
Denna situation inspirerade det vetenskapliga samfundet att hitta nya alternativ för att bekämpa sjukdomen. År 1934... (More)
Malaria är en sjukdom som överförs av myggor; det har överförts påverka mänskligheten i mer än 10 000 år, det påverkar mellan 700 000 och 2,7 miljoner människor per år och det kan vara dödligt, därför finns det ett stort och ökat intresse för att utveckla en bot mot den.
Quinin, den första antimalarialen, isolerades från chinchona-trädet år 1632. Denna förening användes i stor utsträckning i form av tonisk vatten, men efteråt observerade man en minskning av dess antimalarial effektivitet och år 1910 drogs slutsatsen att denna situation berodde på att parasit som orsakar malaria hade utvecklat ett motstånd mot quinin.
Denna situation inspirerade det vetenskapliga samfundet att hitta nya alternativ för att bekämpa sjukdomen. År 1934 utvecklades klorokin av tyska forskare och var den mest använda antimalarialen till 1950-talet, när parasitmotståndet upprepades. Andra läkemedel som mefloquin och arteminisin har utvecklats men resistansproblemet finns fortfarande och därmed bibehåller intresse för utveckling av nya behandlingar.
Framgången av anticancermedicin cisplatin och andra metallbaserade läkemedel har ökat intresse för oorganisk medicinsk kemi. Därför kom forskare till idén om att koppla en känd antimalariell med en organometallisk art och därigenom skapa organometalliska antimalariella komplex som inte bara är effektiva, utan parasiten utvecklar inte motstånd mot den. Studier av ferroquin, ett kloroquinolinderivat kopplat till en ferrocenmolekyl, visade fantastiska resultat och ligger i fas IIb av medicinska prövningar.
Kloroquinderivaten kan kopplas med metaller som rutenium, järn, iridium och rodium, och de första studierna visade liknande resultat (ökad antimalariell aktivitet utan motstånd) mot de från ferroquinstudierna, vilket indikerar den stora framtiden och potentialen hos dessa föreningar. Denna kemi finns fortfarande i utvecklingsfasen. (Less)
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author
Silva Quintero, Maria Alejandra LU
supervisor
organization
course
KEMR12 20162
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8949779
date added to LUP
2018-09-25 11:31:21
date last changed
2018-09-25 11:31:21
@misc{8949779,
  abstract     = {Malaria is a disease that is transmitted by mosquitoes; it has been transmitedaffecting humanity for more than 10.000 years, it affects between 700 000 and 2.7million people per year and it can be deadly, therefore there is a large and increasinginterest in developing a cure against it.

Quinine, the first antimalarial, was isolated from the chinchona tree in 1632. Thiscompound was widely used in the form of tonic water, but afterwards, a decrease ofits antimalarial effectivity was observed and in 1910 it was concluded that thissituation was because the parasite that causes malaria had developed a resistanceagainst the quinine.

This situation inspired the scientific community to find new options to fight thesickness. In 1934, chloroquine was developed by German scientists and was themost used antimalarial until the 1950's, when parasitic resistance again occurred.Other medicaments like mefloquine and arteminisin have been developed but theresistance problem still exists thus maintaining interest in the development of for newtreatments.
The success of the anticancer medicine cisplatin and other metal-based drugs hasincreased interest in inorganic medicinal chemistry. Therefore scientists came to theidea of coupling a known antimalarial with a organometallic species thus creatingorganometallic antimalarial complexes that are not only effective but the parasitedoes not develop resistance against it. Studies of ferroquine, a chloroquinolinederivative coupled with a ferrocene molecule, showed fantastic results and it is inphase IIb of medical trials.

Chloroquine derivatives may be coupled with metals like ruthenium, iron, iridium andrhodium, and the first studies showed similar results (increased antimalarial activitywithout the resistance) to those from the ferroquine studies, indicating the greatfuture and potential of these compounds. This chemistry is still on in the developmentphase.

This project is involved with the development of organometallic antimalarialcompounds. Specifically ruthenium-chloroquine complexes coupled with a water-soluble phosphine molecule (PTA) were targeted in order to create antimalarialcomplexes with good aqueous solubility, which may be of importance to, theirantimalarial effectivity},
  author       = {Silva Quintero, Maria Alejandra},
  language     = {eng},
  note         = {Student Paper},
  title        = {PTA Ruthenium-aminochloroquinoline complexes: Antimalarials of the future},
  year         = {2017},
}