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Antiprotozoal agents. Dr Moustafa K Soltan. Classification of Antiprotozoal agents. antiparastic. antiprotozoal anthelmintics unicellular parasites multicellular parasites . Protzoal infections may be one or more infection results from the following:
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Antiprotozoal agents Dr\ Moustafa K Soltan
Classification of Antiprotozoal agents. antiparastic antiprotozoal anthelmintics unicellular parasites multicellular parasites . Protzoal infections may be one or more infection results from the following: 1) amoebiasis. 2) trichomoniasis. 3) girdiasis. 4) leishmaniasis. 5) trypanosomiasis. 6) malaria. 7) toxoplasmosis. Classification of antiprotozoal infections: I] Antiamoebic drugs. For treatment of Entamoeba histolytica infections. Tissue amoebicides (hepatic amoebiasis ) Extraintestinal amoebicides Act in extraintestinal tissues, in liver, bowel wall they include:nitroimmidazole. : metronidazole, tinidazole , secnidazole. chloroquine: antimalarial emetine, dehydroemetine antibiotic amoebicides: paromomycin
luminal amoebicides :intestinal amoebicides. act in bowel lumen (intestine) they include: halogenated 8-hydroxy quinoline: Chiniofon, clioquinol, iodoquinol. dichloroacetamide derivatives: diloxanide furoate organoarsenicals: carbarsone. II] Antitrichomonal and antigiardial agents are some antiamoebic agents……. III] Antileishmanial drugs: 1) antimonial drugs: sodium stipogluconate. 2) diamidines: pentamidine isothionate. IV] Antitrypanosomal drugs: (trypanocides) 1) 5-nitrofuran derivatives: nifurtimox 2) urea derivatives: suramin sodium. V] antimalarial drugs.
Nitroimmidazole.metronidazole • 2-methyl-5-nitro-1-(2-hydroxyethyl) immidazole.. • Or • 2-(2-methyl-5-nitro-1-immidazolyl) ethanol. • Tinidazole = • 2-methyl-5-nitro-1-[2-(2-ethylsulfonyl) ethyl] immidazole. • Secnidazole: • 2-methyl-5-nitro-1-(2-hydroxypropyl)- immidazole. (or) • 1-(2-methyl-5-nitro-1-immidazolyl)-2-hydroxypropane.
selectivity of nitro group containing antibacterial, antiamoebic, antitrypanosomal arises from absence of nitroreudctase in human and presence of it in the invading organism. 2) so we can say that in metronidazole, tinidazole, secnidazole, nitro group cause both the activity and selectivity. 3) advantages of tinidazole and secnidazole over metronidazole 1) less incidence of side effects. 2) administered single dose daily for 4 days due to high T1/2, while metronidazole 7-10 days. Mechanism of action. Reduction of nitro group by nitroreductase enzyme to unstable, cytotoxic intermediate, interact with DNA prevent further replication so death.* so we can say nitro group is essential for activity. Uses. 1) Intestinal and extraintestinal antiamoebic. 2)antitrichomonal,antigiardial,antileishmanial 3)anaerobic bacteria cause septicemia.*tinidazole has fewer side effects than metronidazole.
2) halogenated 8-hydroxy quinoline Chiniofon :Sodium salt of 7-iodo-8-hydroxuquinoline-5-sulfonate Iodoquinol :5,7-diiodo-8-hydroxyquinoline
Skraup synthesis of quinoline ring: begin from it when asked in synthesis of halogenated 8-hydroxy quinoline derivatives: ( chiniofon, iodoquinol begin from oxine) ( clioquinol begin from 5-chlorooxine) role of conc. H2SO4: Converting glycerol into acrolien which react with o-aminophenol. We can not use acrolein directly as it is toxic compound. role of nitrobenzene: oxidation of 1,2-dihydroquinoline to quinoline ring and reduced to aniline. role of ferrous sulfate: preventing explosion of the reaction.
Clioquinol : 5-chloro-7-iodo-8-hydroxyquinoline 3) dichloroacetamide derivatives Diloxanide furoate :4-(2,2-dichloro-N-methylacetamido)phenyl-2-furoate
Mechanism of action Chelating properties of 8-hydroxyquinoline which bind ferrous atom inside cell Uses: 1)intestinal amoebiasis but cause neurotoxicity. 2) antibacterial, antifungal activity so in skin diseases like dermatitis, eczema, psoriasis (Clioquinol) Uses of Diloxanide intestinal amoebiasis, drug of choice in case of asymptomatic amoebiasis (carriers)
4) organoarsenicals Carbarsone:4-ureido-1-phenyl arsonic acid or 4-carbamoyl amino phenyl arsonic acid or N-carbamoyl arsanilic acid. Or p-uriedobenzene arsonic acid. As+5 is reduced to As+3 which interact with thiol Group of enzymes present in the parasite through complexation reaction leading to death. It acts on trophozite phase of Entamoeba. Used in intestinal amoebiasis.
Antileishmanial drugs. Sodium Stipogluconate: Antimony sodium Gluconate.
Pentamidine Isothionate. ** 4,4- -(pentamethylenedioxy) dibenzamidino-bis- (2-hydroxyethanesulfonate).
Sod stipgluconate Sb+5 is reduced to Sb+3 which inhibit phosphofructokinase enzyme in parasite Drug of choice in treatment of leishmania Pentamidine isothionate 1) interact with DNA resulting in inhibition of DNA, RNA and protein synthesis.2)interfere with polyamine uptake due to structure similarity. 1)alternative for visceral leishmaniasis. 2)2ry agent in treatment, prophylaxis against African trypanosomiasis.
Antitrypanosomal. Nifurtimox: 4-[(5-nitrofufurylidene)amino]-3-methylthiomorpholine-1,1-dioxidex : Suramin sodium :Hexasodium carbonyl-bis-{8-[3-(3-aminobenzamido)-4-methylbenzamido] Naphthalene-1,3,5-trisulfonate}
Uses South American trypanosomiasis which is called ( chagas disease) caused by Trypanosome cruzi (in early stage) Suramin sodium Inhibit various trypanosomal enzymes such as Glycerol-3-phosphate oxidase, so block glycolysis in parasite which depend on glycolysis for energy production so death. Drug of choice in the prophylaxis against African trypanosomiasis in early stages
