Inhibition of phosphatidylcholine biosynthesis and cell proliferation in trypanosomacruzi by ajoene, an antiplatelet compound isolated from garlic

Urbina, Julio A.; Marchán, Edgar; Lazardi, Keyla; Visbal, Gonzalo; Apitz‐Castro, Rafael; Gil, Francisco Javier Martín; Aguirre, Tania; Piras, Marta M.; Piras, Romano

doi:10.1016/0006-2952(93)90217-k

Cited by 68 publications

(40 citation statements)

References 30 publications

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“…The minimal concentration of albaconazole required to induce epimastigote lysis was 30 nM, which is 33 times lower than that of ketoconazole, D0870, or itraconazole and which is comparable to that of posaconazole, the most potent EBI known against this parasite. Furthermore, against the clinically relevant intracellular amastigote form, the minimal concentration required to eliminate the parasite was just 10 nM (16,17,29,30,31,32). These data suggest that albaconazole could be a good candidate for in vivo chemotherapeutic studies.…”

Section: Discussionmentioning

confidence: 85%

Activity of the New Triazole Derivative Albaconazole against Trypanosoma ( Schizotrypanum ) cruzi in Dog Hosts

Guedes¹,

Urbina

Lana³

et al. 2004

Antimicrob Agents Chemother

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Albaconazole is an experimental triazole derivative with potent and broad-spectrum antifungal activity and a remarkably long half-life in dogs, monkeys, and humans. In the present work, we investigated the in vivo activity of this compound against two strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease, using dogs as hosts. The T. cruzi strains used in the study were previously characterized (murine model) as susceptible (strain Berenice-78) and partially resistant (strain Y) to the drugs currently in clinical use, nifurtimox and benznidazole. Our results demonstrated that albaconazole is very effective in suppressing the proliferation of the parasite and preventing the death of infected animals. Furthermore, the parasitological, PCR, serological, and proliferative assay results indicated parasitological cure indices of 25 and 100% among animals inoculated with T. cruzi strain Y when they were treated with albaconazole at 1.5 mg/kg of body weight/day for 60 and 90 days, respectively. On the other hand, although albaconazole given at 1.5 mg/kg/day was very effective in suppressing the proliferation of the parasite in animals infected with the Berenice-78 T. cruzi strain, no parasitological cure was observed among them, even when a longer treatment period (150 doses) was used. In conclusion, our results demonstrate that albaconazole has trypanocidal activity in vivo and is capable of inducing radical parasitological cure, although natural resistance to this compound was also indicated. Furthermore, the compound can be used in long-term treatment schemes (60 to 150 days) with minimal toxicity and thus represents a potentially useful candidate for the treatment of human Chagas' disease.

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Section: Discussionmentioning

confidence: 85%

Activity of the New Triazole Derivative Albaconazole against Trypanosoma ( Schizotrypanum ) cruzi in Dog Hosts

Guedes¹,

Urbina

Lana³

et al. 2004

Antimicrob Agents Chemother

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“…Druggable pathways that interact with sterol metabolism also represent complementary targets. Glycerophospholipid biosynthesis inhibitors, such as ajoene or alkyl-lysophospholipids (ALP, e.g., miltefosine), have been shown to have antiproliferative effects on T. cruzi epimastigotes and amastigotes [20][21][22]. Growth inhibition correlated with a decrease in the phosphatidylcholine to phosphatidylethanolamine ratio (PC:PE) and, in the case of ALP, also with a marked effect on sterol composition due to inhibition of sterol 22-desaturase (Erg5), a finding that probably explains the antiproliferative synergism of these drugs with the Cyp51 inhibitor ketoconazole against both proliferative stages (epimastigotes and intracellular amastigotes) of the parasite [21,22].…”

Section: Quo Vadis Posaconazole?mentioning

confidence: 99%

Match-making for posaconazole through systems thinking

Fügi

Kaiser

Tanner

et al. 2015

Trends in Parasitology

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“…Another example of metabolism inhibition is the growth inhibition of T. cruzi epimastigote caused by ajoene ( Figure 13), a derivative of garlic that can be attributed to changes in the phospholipid composition of the parasite membrane. One of the evidences for these alterations is the low levels of phosphatidylcholine detected, followed by high levels of its immediate precursor, phosphatidylethanolamine, suggesting that ajoene inhibits the final stage of phosphatidylcholine biosynthesis, altering the phospholipid composition of the cell membrane (Urbina et al, 1993). The peroxide group present in some monoterpenes is important for the activity of these compounds.…”

Section: Essential Oils: Mode Of Action Against Trypanosoma Cruzimentioning

confidence: 99%