Trypanocidal effect

The in vivo antitumor and trypanocidal effects of dimeric [Irn2(CH3COO)4(L)ra]° (L = classical organic antimalarial drugs, n= 1, 2) are reported.494 The dimeric complexes are characterized by IR spectroscopy. Further studies of monomeric Ir11 complexes, IrnL2, where L = alkyl or aryl dithiocarbamates and xanthates, reveal no clear relation between antitumor and antitrypanosomal actvities.495 Structure-activity data for the Ir11 complexes is presented. 

Atawodi, S.E. Bulus, T. Ibrahim, S. Amed, D.A. Nok., A.J. Mannnan, M. Galadima, M. In vitro trypanocidal effect of methanolic extract of some Nigerian savarmah plants. African Journal of Biotechnology. 2003, 2, 317-321. 

Nok AJ, Ibrahim S, Arowosafe S, Longdet I, Ambrose A, Onyenekwe PC, Whong CZ (1994) The trypanocidal effect of Cannabis sativa constituents in experimental animal trypanosomiasis. Vet Hum Toxicol 36 522-524... 

For Latin American countries comprising Amazonian areas, development of their vast wilderness regions has become a national priority. The family Compositae has been widely used as medicinal plants in Latin American and their antiparasitic properties are well known. Reports on the protozoocidal activity of the genus Baccharis, a member of the Compositae, are recorded in the literature. Rojas de Arias et al. [97] investigated the trypanocidal effect of crude extracts of some Paraguayan Compositae on the bloodstream forms of... 

Rubin, B. A. The trypanocidal effect of antibiotic lactones and of their analogs. Yale J. Biol, and Med. 20, 233 (1948). 

Biosynthesis of polyamines is essential for growth and multiplication of T. brucei, hence discovery of drug candidates that inhibit enzymes in the polyamine biosynthesis pathway represent an attractive approach to development of trypanocides. The consequences of gene knockout of ornithine decarboxylase (ODC), the target of eflornithine (3), have been further characterized and suggest that new inhibitors of this enzyme may be particularly effective [18]. 

The medicinal use of arsenic compounds is now very limited, but some are still used in human trypanosomiasis. The effect of heterocyclic groups in reducing toxicity is well shown in the trypanocide melarsoprol (Mel B) (263), in which the severe toxicity of sodium arsanilate (atoxyl) has been reduced successively by substitution with a triazine residue and incorporation of the arsenic atom in a heterocycle. 

Radiosensitizing effect in hypoxic cells [89] toxicity to hypoxic cells [102, 112, 115, 116] DNA damage [112], antitrichomonal activity [137], structure-activity [115, 116] inhibition of T. cruzi growth at concentrations that do not stimulate 0 and H202 production (reduced metabolites of benznidazole are involved through covalent binding to macromolecules in its trypanocidal and toxic effects) [133]... 

Effective trypanocidal drugs have been available for 35 years, but because of their expense, toxicity and now resistance to them, the only sure way to eliminate the disease completely is considered to be by vector eradication (2 ). A more realistic approach adopted in West Africa (3) is aimed at introducing trypanotolerant breeds of livestock in areas where the challenge from infected flies is not unduly high. 

Besides the discussed types of biological properties, OTCs showed different kinds of biocidal activity, e.g. trypanocidal , herbicidal , insecticidal (larvicidal and ovicidal ) they have also toxic effects on fresh water and marine algae . 

Suramin is a trypanocide that has been used in the treatment of African trypanosomiasis and onchocerciasis, and has been studied in AIDS (SEDA-10, 277) (SEDA-15, 335). However, the high doses that are required for a worthwhile effect are extraordinarily toxic. It is particularly likely to cause adverse effects in the malnourished and has therefore largely been abandoned for the treatment of trypanosomiasis and onchocerciasis, but it still seems uniquely capable of killing the adult onchocerciasis worm, although results are sometimes incomplete even in that respect (SEDA-20, 283). 

Mercier-Parot L, Tuchmann-Duplessis H. Action abortive et teratogene d un trypanocide, la suramine. [Abortifacient and teratogenic effect of suramin, a trypanocide.] C R Seances Soc Biol Fil 1973 167(ll) 1518-22. 

Zagana P, Klepetsanis P, loannou PV, Loiseau PM, Antimisiaris SG (2007) Trypanocidal activity of arsonoliposomes effect of vesicle lipid composition. Biomed Pharmacother 61 499-504... 

Biological effects antitumor (Section 8.1), antifungal and antibacterial (Section 8.2), trypanocidal (Section 8.3.1), leishmanicidal (Section 8.3.2). 

The most important trypanocidal furan is nitrofurazone which will cure T. equiperdum infections in laboratory animals. It is effective against T. equiper-dum in 20 hours at a concentration of 1 -2 [rg/ml. and T. rhodensiense in vitro. In vivo curative dose (CDgj) for T. equiperdum in mice is 248 mg/kg if the... 

Disruption of AdoMet metabolism is a key element also in the action of 5 - [(Z)-5-amino-2-butenyl]methylamino 5 -deoxyadenosine (MDL73811), an AdoMet decarboxylase inhibitor which is a highly effective trypanocide (53). Treatment of trypanosomes with MDL73811 caused a 20-fold increase in the trypanosome AdoMet level after only 1 h of exposure. In comparison, AdoMet levels in cultured mammalian cells rose only 1.5-fold after similar treatment with MDL73811 (48). This analog is rapidly concentrated by trypanosomes through the purine transport system (54). 

In African trypanosomes this enzyme also cleaves 5 -halo- and ethylthioribose derivatives of MTA to produce adenine plus the resulting ribose analog (74). The latter would normally be recycled to methionine (5). These agents are trypanocidal and their effects can be reversed with methionine or ketomethylthiobutyrate, an intermediate in the conversion of methylthioribose into methionine (74). 

ANTIPROTOZOAL EFFECTS Nifurtimox and benznidazole are trypanocidal against both the trypomastigote and amastigote forms of T. cruzi. Nifurtimox also has activity against T. brucei and can cure early- and late-stage disease. 

Nifurtimox is well absorbed after oral administration, with peak plasma levels observed after 3.5 hours. Less than 0.5% of the dose is excreted in urine. The elimination t is 3 hours. High concentrations of several unidentified metabolites are found, and nifurtimox undergoes rapid biotransformation, probably via a presystemic first-pass effect. Whether the metabolites have any trypanocidal activity is unknown. 

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