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Content:
Introduction
History
Chemistry of artemisinin
Structural activity relationship of artemisinin
Mechanism of action
Drug interactions
Malaria is a very common disease. This probably originated in Africa around 30 million years ago.
 In 1600s first treatment to malaria was recorded in Peru where native tribes used bitter bark of cinchona, to reduce the fever and pain.
In 1897 Sir Ronald Ross described female anopheles mosquito as the vector of the disease.
In 1950s the disease rebounded largely due to emergence of parasites resistant to drugs like chloroquine.
In 1967 a plant screening research program code named “Project 523” was set up in China by the People’s liberation army ordered by Mao Zedong at the request of North Vietnamese.
Under able leadership of Dr. Y. Tu more than 2000 herbs preparations were investigated . Out of which 640 herbs were hits.
The turning point came when Sweet wormwood extract showed a promising degree of inhibition in mouse model.
Although the progress was not smooth as the observation was not reproducible in subsequent experiments.
During cultural revolution no clinical trials were performed so Dr. Tu bravely volunteered to the first trials.
In Hainan first official trials happened on malaria patients. The patients showed much better result than chloroquine (Test samples).
Encouraged by this outcome, she moved on to investigate and isolated the pure compound of Artemisia.
In 1972 a colorless crystalline substance with a mol wgt. of 282 Da, having molecular formula of C15H22O5 was isolated. The molecule was named as Qinghau su (Artemisinin) from the leaves of Sweet wormwood scientifically known as Artemisia annua, family Compositae.
Dr. Y. Tu was awarded with Lasker DeBakey clinical medical research award in 2011 and finally the Nobel Prize in physiology and medicine of artemisinin in 2015.
SAR OF ARTEMISININ
Tetracyclic structure with a trioxane ring and a lactone ring.
Trioxane ring contains a peroxide bridge, the active moiety of the molecule. 
 MOL. FORMULA: C15H22O5; MOL .MASS: 282.332
Presence of a ‘Trioxane’ moiety which consists of the endoperoxide & doxepin oxygens that is evidently displayed by a simplified version of 3- aryltrioxanes.
Modification of 10th position ‘C’ gives a powerful derivative compared to the original compound.
Reduction of artemisinin to dihydroartemisinin gives rises to a chiral centre that may ultimately lead to the formation of prodrugs.
Artemisinin is a poorly soluble in oils and water so it is administered through oral, IM or rectal route.
Semi synthetic like artesunate, artemether arteether and hemisuccinate ester were produced because of poor bioavailability and limit of its effectiveness.
To stop the malarial activity, the target was a retroviral aspartyl protease which can be found in the plasmodium faliciparum parasite.
The metabolite dihydroartemisinin cleaves the endoperoxide ring inside the erythrocyte.

Content:
Introduction
History
Chemistry of artemisinin
Structural activity relationship of artemisinin
Mechanism of action
Drug interactions
Malaria is a very common disease. This probably originated in Africa around 30 million years ago.
 In 1600s first treatment to malaria was recorded in Peru where native tribes used bitter bark of cinchona, to reduce the fever and pain.
In 1897 Sir Ronald Ross described female anopheles mosquito as the vector of the disease.
In 1950s the disease rebounded largely due to emergence of parasites resistant to drugs like chloroquine.
In 1967 a plant screening research program code named “Project 523” was set up in China by the People’s liberation army ordered by Mao Zedong at the request of North Vietnamese.
Under able leadership of Dr. Y. Tu more than 2000 herbs preparations were investigated . Out of which 640 herbs were hits.
The turning point came when Sweet wormwood extract showed a promising degree of inhibition in mouse model.
Although the progress was not smooth as the observation was not reproducible in subsequent experiments.
During cultural revolution no clinical trials were performed so Dr. Tu bravely volunteered to the first trials.
In Hainan first official trials happened on malaria patients. The patients showed much better result than chloroquine (Test samples).
Encouraged by this outcome, she moved on to investigate and isolated the pure compound of Artemisia.
In 1972 a colorless crystalline substance with a mol wgt. of 282 Da, having molecular formula of C15H22O5 was isolated. The molecule was named as Qinghau su (Artemisinin) from the leaves of Sweet wormwood scientifically known as Artemisia annua, family Compositae.
Dr. Y. Tu was awarded with Lasker DeBakey clinical medical research award in 2011 and finally the Nobel Prize in physiology and medicine of artemisinin in 2015.
SAR OF ARTEMISININ
Tetracyclic structure with a trioxane ring and a lactone ring.
Trioxane ring contains a peroxide bridge, the active moiety of the molecule. 
 MOL. FORMULA: C15H22O5; MOL .MASS: 282.332
Presence of a ‘Trioxane’ moiety which consists of the endoperoxide & doxepin oxygens that is evidently displayed by a simplified version of 3- aryltrioxanes.
Modification of 10th position ‘C’ gives a powerful derivative compared to the original compound.
Reduction of artemisinin to dihydroartemisinin gives rises to a chiral centre that may ultimately lead to the formation of prodrugs.
Artemisinin is a poorly soluble in oils and water so it is administered through oral, IM or rectal route.
Semi synthetic like artesunate, artemether arteether and hemisuccinate ester were produced because of poor bioavailability and limit of its effectiveness.
To stop the malarial activity, the target was a retroviral aspartyl protease which can be found in the plasmodium faliciparum parasite.
The metabolite dihydroartemisinin cleaves the endoperoxide ring inside the erythrocyte.

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ARTEMISININ presentation .pptx

  1. 1. ARTEMISININ PRESENTED BY: Ms Himani K S 1st M Pharm Dept. of Pharmaceutical Chemistry Jss College of Pharmacy, Mysore PRESENTED TO: Dr G V Pujar Professor & Vice Principal Dept. of Pharmaceutical Chemistry Jss College of Pharmacy, Mysore
  2. 2. CONTENT • Introduction • History • Chemistry of artemisinin • Structural activity relationship of artemisinin • Mechanism of action • Drug interactions
  3. 3. INTRODUCTION AND HISTORY • Malaria is a very common disease. This probably originated in Africa around 30 million years ago. • In 1600s first treatment to malaria was recorded in Peru where native tribes used bitter bark of cinchona, to reduce the fever and pain. • In 1897 Sir Ronald Ross described female anopheles mosquito as the vector of the disease. • In 1950s the disease rebounded largely due to emergence of parasites resistant to drugs like chloroquine. • In 1967 a plant screening research program code named “Project 523” was set up in China by the People’s liberation army ordered by Mao Zedong at the request of North Vietnamese.
  4. 4. HISTORY • Under able leadership of Dr. Y. Tu more than 2000 herbs preparations were investigated . Out of which 640 herbs were hits. • The turning point came when Sweet wormwood extract showed a promising degree of inhibition in mouse model. • Although the progress was not smooth as the observation was not reproducible in subsequent experiments. • During cultural revolution no clinical trials were performed so Dr. Tu bravely volunteered to the first trials. • In Hainan first official trials happened on malaria patients. The patients showed much better result than chloroquine (Test samples).
  5. 5. HISTORY • Encouraged by this outcome, she moved on to investigate and isolated the pure compound of Artemisia. • In 1972 a colorless crystalline substance with a mol wgt. of 282 Da, having molecular formula of C15H22O5 was isolated. The molecule was named as Qinghau su (Artemisinin) from the leaves of Sweet wormwood scientifically known as Artemisia annua, family Compositae. • Dr. Y. Tu was awarded with Lasker DeBakey clinical medical research award in 2011 and finally the Nobel Prize in physiology and medicine of artemisinin in 2015.
  6. 6. CHEMISTRY OF ARTEMISININ Formula C15H22O5 Molar mass 282.336 g·mol−1 IUPAC name (3R,5aS,6R,8aS,9R,12S,12aR)-Octahydro-3,6,9-tri methyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodio xepin-10(3H)-one
  7. 7. SAR OF ARTEMISININ • Tetracyclic structure with a trioxane ring and a lactone ring. • Trioxane ring contains a peroxide bridge, the active moiety of the molecule. • MOL. FORMULA: C15H22O5; MOL .MASS: 282.332 • Presence of a ‘Trioxane’ moiety which consists of the endoperoxide & doxepin oxygens that is evidently displayed by a simplified version of 3- aryltrioxanes. • Modification of 10th position ‘C’ gives a powerful derivative compared to the original compound.
  8. 8. SAR OF ARTEMISININ • Reduction of artemisinin to dihydroartemisinin gives rises to a chiral centre that may ultimately lead to the formation of prodrugs. • Artemisinin is a poorly soluble in oils and water so it is administered through oral, IM or rectal route. • Semi synthetic like artesunate, artemether arteether and hemisuccinate ester were produced because of poor bioavailability and limit of its effectiveness.
  9. 9. MECHANISM OF ACTION • To stop the malarial activity, the target was a retroviral aspartyl protease which can be found in the plasmodium faliciparum parasite. • The metabolite dihydroartemisinin cleaves the endoperoxide ring inside the erythrocyte. The drug molecule come in contact with haem and the ferric oxide breaks the endoperoxide rings. • This produces free radicals to damage the susceptible protein to kill the parasite.
  10. 10. DRUG INTERACTIONS • Chloroquine and pyrimethamine may antagonise the activity of artemisinin whereas mefloquine, quinine,primaquine and tetracycline potentiate artemisinin. • The combination of artemisinin derivatives and mefloquine improves parasite clearance compared with either drug alone.
  11. 11. REFERENCE • Burger’s medicinal chemistry and drug discovery sixth edition, volume 1: Drug discovery. • https://en.m.wikipedia.org/wiki/Artemisinin#:~:text=Artemisinin%20(%2F %CB%8C%C9%91%CB%90t%C9%AA,or%20Medicine%20for%20her %20discovery. • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671478/

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