Amoebicides

There is a voluminous literature on the subject of amoebicidal agents, which is summarised up to 1932 by Fischl and Schlossberger. Recent work includes the clinical comparison by Manson-Bahr of a number of possible substitutes for emetine, the introduction of improved methods for the biological testing of potential amoebicides of which the papers by Jones and by Goodwin, Hoare and Sharp afford examples, and work... 

Coulthard for amoebicidal action. Each kind of activity increases to a peak as the series is ascended and then diminishes. In the 0-n-alkyl series the peak is at 0-n-butylharmol for Bacillus typhosus, at 0-n-amyl-harmol for Staphylococcus aureus and at 0-n-nonylharmol for Entamoeba histolytica. In the 0-io-diethylaminoalkyl series the peak for B. typhosus is at 0-to-diethylaminononylharmol. No trypanocidal or anti-malarial action was observed in a selection of the compounds tested. ... 

Paromomycin finds special use in the treatment of intestinal amoebiasis (it is amoebicidal against histolytica) and of acute bacillary dysentery. 

A. L. Elias, J. C. Carrero-Sanchez, H. Terrones, M. Endo, J. P. Laclette, M Terrones, Viability studies of pure carbon- and nitrogen-doped nanotubes with Entamoeba histolytica From amoebicidal to biocompatible structures, Small, vol. 3, pp. 1723-1729, 2007. 

Leon-Sicairos, N., Lopez-Soto, F., Reyes-Lopez, M., Godinez-Vargas, D., Ordaz-Pichardo, C., and de la, G. M. (2006). Amoebicidal activity of milk, apo-lactoferrin, sIgA and lysozyme. Clin. Med. Res. 4,106-113. 

Metronidazole is a nitro-imidazole. It is a mixed amoebicide, i.e. it acts at all sites of infection. It has to be activated in the parasite. By reduction in the amoeba of its nitro group reactive intermediates are formed, resulting in oxidative damage and ultimately cell kill. It is effective against many parasitic intestinal and tissue infections such as trichomoniasis, giardiasis and amoebiasis. It is the drug of choice for amoebic dysentery and amoebic liver abscess. 

Of the dichloroacetamides diloxanide furoate, clefamide, teclozan and etofamide the most frequently used agent is diloxanide furoate. It is the luminal amoebicide of choice in chronic intestinal amoebiasis, however it lacks efficacy acute intestinal amoebiasis. Its mechanism of action is unknown. Given orally, diloxanide is formed by bacterial hydrolases. Diloxanide is for 90% absorbed and then metabolized to diloxanide glucuronide. The remaining 10% remains in the intestine as the active drug. Diloxanide is generally well tolerated. Adverse effects include flatulence, nausea and abdominal cramps. 

Diloxanide furoate is the furoate ester of 2,3-dichloro-4-hydroxy-A-methyl acetanilide. This antiamoebic drug was developed as a result of the discovery that various a,a-dichloroacetamides possessed an amoebicidal activity [1]. Diloxanide furoate is considered as a safe and effective drug for the treatment of asymptotic or mildly symptomatic persons who are passing cysts of Entameba histolytica [2,3], It acts principally in the bowel lumen, and is used in the treatment of the intestinal amoebiasis. It is less effective in amebic dysentery than in asymptotic infection, but the furoate gives high intestinal concentrations and is possibly more effective than metronidazole in the treatment of cyst passers [4],... 

Quiniodochlor is found effective against dermatophytosis, infected eczema and seborrhoeic dermatitis. Orally it is used as luminal amoebicide. 

Diiodohydroxyquinoline is directly amoebicidal. It has activity against motile and cystic forms. It kills cyst forming trophozoites in intestine but has no tissue amoebicidal action. It is ineffective in extraintestinal amoebiasis. It is also effective in cyst passing patients. 

It is a dichloroacetamide derivative, very effective luminal amoebicide. Used alone for cyst passers or usually with metronidazole for other forms of amoebic infections. 

It is an aminoglycoside antibiotic used only as luminal amoebicide and has no effect against extra intestinal amoebic infections. It is less toxic than other agents, but it should be used cautiously in patients with significant renal disease and with gastrointestinal ulcer. 

Phenanthroline inhibits proline incorporation into proteins.391,392 Benzo-substituted-l,8-phenanthrolines and 1,10-phenanthrolines are amoebicides.180 l,8-Phenanthroline-8-oxide has a wide spectrum of antibacterial activity.393... 

The most important biologically active 4,7-phenanthroline is 4,7-phenanthroline-5,6-dione (112), known as phanquone, Entobex, which is used medicinally as an amoebicide. It is active also against bacteria, protozoa, and other parasites.390 Several closely related derivatives are also highly active.224, 250, 251,258-261, 390,538,539 Phanquone is used particularly in treating amoebic dysentery and is often used in combination with other antibiotics.540-542 The effect of 4,7-phenanthroline-5,6-dione and its relatives on cell metabolism has been investigated.543 It has also been reported to be mutagenic.544... 

The antidiarrhoeal drug ipecac, which was introduced into Europe from Brazil in 1658, contains the amoebicidal alkaloids emetine (12) and cephaeline. Emetine remained the major remedy for amoebic dysentery and amoebic hepatitis for many years. Cephaeline is less active and more toxic. ( j-2-Dehydroemetine, which is made by synthesis, is equiactive with (—)-emetine and less toxic, but other chemical modification has not yielded better amoebicides. From investigations of synthetic routes to the benzoquinolizine moiety the tranquilizer tetrabenazine (13a) was discovered. The very similar compound benzquinamide (13b) is also a tranquilizer and antiemetic. 

They are still used in the treatment of other parasitic infections. Thus, derivatives of benzene arsonic acid, CsHsAsOfOH, such asiV-acetyl-4-hydroxy-m-arsanilic acid, Af-carbamoylarsanilic acid and its oxide, sodium -(carbamoyl-methyl) arsanilate and glycobiarsol (18) are potent intestinal amoebicides when taken orally, and difetarsone (19) has recently found use as an anthelminthic29. They are also administered in the treatment of trypanosomiasis and helminthiasis in animals, as well as in topical application to destroy Trichomonas vaginalis and moni-linia. For the first of these purposes they have been largely replaced by melarsoprol... 

Only with PhS ions and A-methylimidazole-2-thiolate ions was the disubstitution product (8-10%) detected. These compounds, among others with the quinoline moiety, have amoebicide activity266. 

S PS - 40S subunit site (cf. Cryptopleurine, Emetine Tvlocrebrine) [amoebicidal, antitumour, toxic]... 

Tubulosine Cephaelis ipecacuanha, Pogonopus [amoebicidal, antitumour,... 

PHMB and chlorhexidine were found to be the most successful cysticidal agents. Neomycin was reported to be ineffective against neomycin, propamidine Acanthamoeba cysts in vivo. The cysticidal effectiveness of propamidine was more variable than its trophozoite amoebicidal activity... 

Hexamidine, propamidine Hexamidine demonstrated greater amoebicidal activity than propamidine. Perrine et al. recommended replacing propamidine with... 

Perrine D, Chenu JP, Georges P, et al. Amoebicidal efficiencies of various diamidines against two stains of Acanthamoeba polyphaga. Antimicrob Agents Chemother 1995 39(2) 339-342. 

This type of cyclization has recendy been used in the caibocyclic field to synthesize the tetracyclic glycol (234), an advanced intermediate in the synthesis of the antimicrobial and amoebicidal agent ikaru-gamycin. Thus photocyclization of a 2 1 mixture of trienes (235) and (236) led to a 4 1 mixture of the two possible conrotatory closure products (237) and (238), which likely reflect the conformational bias in the ground state of the (20-triene (23fo and 236b, respectively). ... 

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