Elshahawi: Antimalarial and anti parasites

Pharmacophore of metronidazole

nitroimidazole

Pharmacophore of tinidazole

nitroimidazole

Nitazoxanide pharmacophore

nitrothiazole

Which nitroimidazole is a prodrug

nitazoxanide

Which nitroimidazole has a distinct MOA

nitazoxanide: disrupts PFOR cycle and inhibits energy metabolism of parasite due it high redox potential

What is the MOA of nitroimidazoles

generates OH free radical that damages DNA

Melarsoprol SAR

arsenic group

Melarsoprol MOA

arsenic binds to free thiol groups of cysteine residues on pyruvate kinase and trypanothione reductase

Albendazole SAR

benzimidazole

Mebendazole SAR

benzimidazole

Which benzimidazole is a prodrug

albendazole

MOA of benzimidazoles

inhibits tubulin polymerization and fumarate reductase (reduces NAD+ for ATP production)

Ivermectin SAR

macrolactone

Moxidectin SAR

macrolactone

Macrolactone MOA

GABA agonist: hyperpolarization of Cl- channels = paralysis

Praziquantel MOA

increases worm cell permeability to calcium = contractions = paralysis

Benznidazole indication

chagas disease

Pyrantel pamoate MOA

depolarizing NMB = activates nicotinic receptors and inhibits cholinergic receptors = paralysis

Which drugs a 4-substituted quinolines

hydroxychloroquine, chloroquine, mefloquine

MOA of 4-substituted quinolines

prevents heme neutralizations and keeps it in the vacuole = toxicity

How is resistance generated for 4-substituted quinolines

P-gp efflux

Lumefantrine SAR

tricyclic with hydroxyl

Lumefantrine is administered in which enantiomer

racemic

Lumefantrine MOA

binds to hematin and plasmepsin (protease)

8-aminoquinolines drugs

primaquine, tafenoquine

Which drugs should be avoided for G6PH deficiency

8-aminoquinolines

Aminopyrimidines MOA

inhibit purine and pyrimidine synthesis

• Sulfadoxine = inhibits DHS

• Pyrimethamine = inhibits DHFR

Aminopyridines drugs

sulfadoxine, pyrimethamine

What is the active form a proguanil

cycloguanil

Naphthoquinone drugs

atovaquone

Atovaquone MOA

inhibits Cytochrome bc1 in parasite ETC

Biguanide drug

proguanil

Proguanil MOA

DHFR inhibitor

Artemisinins SAR

endoperoxide bridge

Artemisinins MOA

gets cleaved by heme and generates free radicals

What antibiotics can be used for malaria

macrolides or doxycycline for prophylaxis or adjuct

8-aminoquinoline sar

Naphthoquinone ring

how does nitazoxanide become active

deacetylation of the acetyl group

the acetyl group is removed via deacetylation