malaria

Question 1

state the history of artemisinin

Answer 1

There are number of drugs that are used for treatment of malaria. A more recent introduction is artemisinin and a number of its derivatives.

Chinese people have used Artemisia annua for over 2000 and has its first use as an antimalarial agent is mentioned in 340 AD. Artemisinin was first isolated in 1972, when tested was found to be effective against Plasmodium falsciparum and with a rapid action against chloroquine sensitive strains.

Question 2

describe the mode of action for artemisinin

Answer 2

Artemisinin antimalarial action is from coupling with haemin (iron-porphyrin released after the parasite digests haemoglobin) with the result that free radicals are generated from the peroxide causing damage to the proteins in the parasite (localised effect).

Question 3

why is artemisinin not toxic to humans

Answer 3

Artemisinin and related compounds are not toxic to humans. This stems from the heme-mediated decomposition leads to selective toxicity for the parasite. Hence are not toxic to humans.

Question 4

can artemisinin be used for malaria prevention? yes or no

explain your answer.

if no how can they be used to battle malaria?

Answer 4

Though, the artemisinins are not used for malaria prophylaxis (prevention) because of the extremely short activity (half-life) of the drug. To be effective, it would have to be administered multiple times each day. However, they are used in combination therapy.

Question 5

explain why the combination therapy of artemisinin ( e.g. artemether and lumefantrine) work?

Answer 5

The WHO has recommended artemisinin combination therapies (e.g. artemether and lumefantrine) be the first-line therapy for P. falciparum malaria worldwide.
Combinations are effective because the artemisinin component kills the majority of parasites at the start of the treatment, while the more slowly metabolised partner drug clears the remaining parasites.

Question 6

what is the major limitation of using artemisinin derivatives and why is this a limitation?

Answer 6

Artemisinin has been obtained from A. annua cultivated in parts of Asia and Africa, until recently. Prices were high and there is the problem to satisfy the worldwide demand. Various methods have been explored to obtain more quantities of artemisinin.

Question 7

list and explain the various methods of extracting artemisinin? what are the limitations if there are any?

Answer 7

Genotypes of the species with high yields, up to 1.5%, have been reported. Tissue culture methods, using the roots of the plant, have not been found to be economically viable. Total chemical synthesis of artemisinin has shown also to be possible using monoterpenes as precursors, such as citronella, pulegone and β-pinene, but the yields were less than 10% and thus not cost effective.

Microbial engineering methods have been applied and have made it possible to obtain suitable intermediates which can then be chemically modified to give artemisinin (a new term is been used to describe this type of process = ‘synthetic biology’) (also see DNA recombinant notes). Artemisinin is produced semi synthetically from artemisinic acid in good amounts using engineered yeast.

Question 8

what class of compound is artemisinic acid?

Answer 8

monocarboxylic acid

Question 9

Dihydroartemisinin Inhibits______

Answer 9

the Proliferation of Leukemia Cells K562 by Suppressing PKM2 and GLUT1 Mediated Aerobic Glycolysis,

Question 10

DHA inhibits_________

Answer 10

leukemia cell proliferation by regulating glycolysis and metabolism, which mediated by downregulating PKM2 and GLUT1 expression.

Question 11

which scientific experiment has been successful for making artemisinin

Answer 11

microbes made to manufacture drugs