Have not read the full journal article yet - available free from pubmed.
This sounds like a promising drug. Babesia parasites rob the body of phosphatidylcholine which is one of the good fats found in the brain and helps form the myelin sheath around nerves. Choline is also very important to liver function.
New insight in the mechanism of accumulation and intraerythrocytic compartmentation of albitiazolium - a new type of antimalarial.
Wein S1, Tran Van Ba C2, Maynadier M2, Bordat Y2, Perez J2, Peyrottes S3, Fraisse L4, Vial HJ5.
Abstract
Bis-thiazolium salts constitute a new class of anti-hematozoan drugs that inhibit parasite phosphatidylcholine biosynthesis. They specifically accumulate in Plasmodium- and Babesia-infected erythrocytes.
Here, we provide new insight on the choline analogue albitiazolium, which is currently clinically tested against severe malaria.
Concentration-dependent accumulation in P. falciparum-infected erythrocytes reached steady-state after 90-120 min and was massive throughout the blood cycle, with cellular accumulation ratios of up to 1000.
This could not occur through a lysosomotropic effect, and the extent did not depend on the food vacuole pH, which is the case for the weak base chloroquine.
Analysis of albitiazolium accumulation in P. falciparum-IRBC revealed a high-affinity component, restricted to mature stages and suppressed by pepstatin A treatment, and thus likely related to drug accumulation in the parasite food vacuole.
Albitiazolium also accumulated in a second high-capacity component present throughout the blood cycle, likely not related to the food vacuole and also observed with Babesia divergens- infected erythrocytes.
Accumulation was strictly glucose dependent, drastically inhibited by H+/K+ and Na+ ionophores upon collapse of ionic gradients and appeared to be energized by the proton-motive force across the erythrocyte plasma membrane, indicating the importance of transport steps for this permanently charged new type of antimalarial.
This specific, massive and irreversible accumulation allows albitiazolium to restrict its toxicity to hematozoan-infected erythrocytes. The intraparasitic compartmentation of albitiazolium corroborates a dual mechanism of action, which could make this new type of antimalarial resistant to parasite resistance.
PMID: 25001307 [PubMed - as supplied by publisher] Free full text
Posts: 7306 | From Martinsville,VA,USA | Registered: Oct 2004
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TNT
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This specific, massive and irreversible accumulation allows albitiazolium to restrict its toxicity to hematozoan-infected erythrocytes.
Wow, this drug sounds wonderful! Sounds very potent without causing the host any toxicity from the drug.
The downside might be a MASSIVE die-off... and that could be toxic!
Thanks, Bea, how did you ever find that so soon after publishing? Regardless, it's good to know someone is working on the problem of drug-resistant protozoans.
Posts: 1308 | From Eastern USA | Registered: Oct 2013
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TNT, I just did a simple pubmed search. I do those every month or so. I generally just do a general search with simple keywords such as babesia or ehrlichia. More advanced searches can be done. But with all searches the most recent publications are listed first.
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