{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:21:17Z","timestamp":1791354077119,"version":"4.3.1"},"reference-count":44,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,10,3]]},"abstract":"We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro<\/jats:italic> and in vivo<\/jats:italic> growths of Babesia<\/jats:italic> parasites. The in vitro<\/jats:italic> growth of Babesia bovis<\/jats:italic>, B. bigemina<\/jats:italic>, B. caballi<\/jats:italic>, and B. equi<\/jats:italic> was significantly inhibited (P<\/jats:italic> < 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 \u03bcM, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 \u03bcM, respectively). Furthermore, both reagents either alone at a concentration of 5 mg\/kg or in combinations (2.5\/2.5 and 5\/5 mg\/kg) for 10 days significantly inhibited the in vivo<\/jats:italic> growth of B. microti<\/jats:italic> in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia<\/jats:italic> parasites.<\/jats:p>","DOI":"10.4269\/ajtmh.2012.12-0218","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T15:15:22Z","timestamp":1348240522000},"page":"681-688","source":"Crossref","is-referenced-by-count":18,"title":["Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites"],"prefix":"10.4269","volume":"87","author":[{"given":"Tserendorj","family":"Munkhjargal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"AbouLaila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad 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Animals and Man","first-page":"1","article-title":"World-wide impact of babesiosis","author":"Kuttler","year":"1988"},{"key":"R2","series-title":"Babesiosis of Domestic Animals and Man","first-page":"99","article-title":"Pathogenesis of babesiosis","author":"Wright","year":"1988"},{"key":"R3","series-title":"Clin Microbiol Rev","first-page":"451","article-title":"Babesiosis","volume":"13","author":"Homer","year":"2000"},{"key":"R4","series-title":"Int J Parasitol","first-page":"1323","article-title":"Human babesiosis: an emerging tick-borne disease","volume":"30","author":"Kjemtrup","year":"2000"},{"key":"R5","series-title":"Vet Parasitol","first-page":"147","article-title":"Chemotherapy against babesiosis","volume":"138","author":"Vial","year":"2006"},{"key":"R6","series-title":"Am J Trop Med Hyg","first-page":"334","article-title":"Growth inhibitory effect of triclosan on equine and bovine Babesia parasites","volume":"68","author":"Bork","year":"2003a"},{"key":"R7","series-title":"Antimicrob Agents Chemother","first-page":"800","article-title":"Growth-inhibitory effects of artesunate, pyrimethamine, and pamaquine against Babesia equi and Babesia caballi in in vitro cultures","volume":"47","author":"Nagai","year":"2003"},{"key":"R8","series-title":"Antimicrob Agents Chemother","first-page":"236","article-title":"Growth-inhibitory effect of heparin on Babesia parasites","volume":"48","author":"Bork","year":"2004"},{"key":"R9","series-title":"Parasitology","first-page":"775","article-title":"Effect of protein kinase inhibitors on the in vitro growth of Babesia bovis","volume":"132","author":"Bork","year":"2006"},{"key":"R10","series-title":"Exp Parasitol","first-page":"214","article-title":"Babesia bovis: effects of cysteine protease inhibitors on in vitro growth","volume":"117","author":"Okubo","year":"2007"},{"key":"R11","series-title":"JEM","first-page":"961","article-title":"Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease","volume":"173","author":"Goldberg","year":"1991"},{"key":"R12","series-title":"Mol Biochem Parasitol","first-page":"303","article-title":"Cloning and characterization of an Eimeria acervulina sporozoite gene homologous to aspartyl proteinases","volume":"62","author":"Laurent","year":"1993"},{"key":"R13","series-title":"Int J Parasitol","first-page":"1099","article-title":"Differential localization of an Eimeria tenella aspartyl proteinase during the infection process","volume":"30","author":"Jean","year":"2000"},{"key":"R14","series-title":"Exp Parasitol","first-page":"128","article-title":"Trypanosoma cruzi: isolation and characterization of aspartyl proteases","volume":"122","author":"Pinho","year":"2009"},{"key":"R15","series-title":"EMBO J","first-page":"306","article-title":"Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase","volume":"13","author":"Francis","year":"1994"},{"key":"R16","series-title":"Proc Natl Acad Sci USA","first-page":"10034","article-title":"Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum","volume":"93","author":"Silva","year":"1996"},{"key":"R17","series-title":"Eur J Biochem","first-page":"552","article-title":"Expression and characterisation of plasmepsin I from Plasmodium falciparum","volume":"244","author":"Moon","year":"1997"},{"key":"R18","series-title":"Proc Natl Acad Sci USA","first-page":"990","article-title":"Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine","volume":"99","author":"Banerjee","year":"2002"},{"key":"R19","series-title":"J Protozool","first-page":"593","article-title":"Plasmodium falciparum: differential sensitivity in vitro to E-64 (cysteine protease inhibitor) and pepstatin A (aspartyl protease inhibitor)","volume":"39","author":"Bailly","year":"1992"},{"key":"R20","series-title":"Antimicrob Agents Chemother","first-page":"2254","article-title":"Antimalarial synergy of cysteine and aspartic protease inhibitors","volume":"42","author":"Semenov","year":"1998"},{"key":"R21","series-title":"J Biochem","first-page":"71","article-title":"Purification and characterization of a hemoglobin degrading aspartic protease from the malarial parasite Plasmodium vivax","volume":"138","author":"Sharma","year":"2005"},{"key":"R22","series-title":"Drugs","first-page":"430","article-title":"Mefloquine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy","volume":"45","author":"Palmer","year":"1993"},{"key":"R23","series-title":"Parasitol Today","first-page":"248","article-title":"Mefloquine resistance in Plasmodium falciparum","volume":"11","author":"Mockenhaupt","year":"1995"},{"key":"R24","series-title":"J Travel Med","first-page":"122","article-title":"Mefloquine for malaria chemoprophylaxis 1992\u20131998: a review","volume":"6","author":"Schlagenhauf","year":"1999"},{"key":"R25","series-title":"Malar J","first-page":"188","article-title":"Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis","volume":"8","author":"Nevin","year":"2009"},{"key":"R26","series-title":"Biochem Pharmacol","first-page":"727","article-title":"An assessment of drug-haematin binding as a mechanism for inhibition of haematin polymerisation by quinoline antimalarials","volume":"55","author":"Dorn","year":"1998"},{"key":"R27","series-title":"Antimicrob Agents Chemother","first-page":"2973","article-title":"Central role of hemoglobin degradation in mechanisms of action of 4-aminoquinolines, quinoline methanols, and phenanthrene methanols","volume":"42","author":"Mungthin","year":"1998"},{"key":"R28","series-title":"PLoS Pathog","first-page":"1401","article-title":"Genome sequence of Babesia bovis and comparative analysis of apicomplexan hemoprotozoa","volume":"3","author":"Brayton","year":"2007"},{"key":"R29","series-title":"Vet Parasitol","first-page":"19","article-title":"Evaluation of the in vitro growth-inhibitory effect of epoxomicin on Babesia parasites","volume":"167","author":"AbouLaila","year":"2010a"},{"key":"R30","series-title":"Parasitol Res","first-page":"355","article-title":"Continuous in vitro cultivation of erythrocytic stages of Babesia equi","volume":"81","author":"Zweygarth","year":"1995"},{"key":"R31","series-title":"Am J Vet Res","first-page":"2059","article-title":"Optimization of the suspension culture method for in vitro cultivation of Babesia bovis","volume":"41","author":"Erp","year":"1980"},{"key":"R32","series-title":"Antimicrob Agents Chemother","first-page":"3196","article-title":"Apicoplast-targeting antibacterials inhibit the growth of Babesia parasites","volume":"56","author":"AbouLaila","year":"2012"},{"key":"R33","series-title":"Parasitology","first-page":"311","article-title":"Clotrimazole, ketoconazole, and clodinafop-propargyl inhibit the in vitro growth of Babesia bigemina and Babesia bovis (Phylum Apicomplexa)","volume":"127","author":"Bork","year":"2003c"},{"key":"R34","series-title":"Malar J","first-page":"10","article-title":"Failure of artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria in southern Cambodia","volume":"8","author":"Rogers","year":"2009"},{"key":"R35","series-title":"J Antimicrob Chemother","first-page":"1387","article-title":"Synergy of mefloquine activity with atorvastatin, but not chloroquine and monodesethylamodiaquine, and association with the pfmdr1 gene","volume":"65","author":"Wurtz","year":"2010"},{"key":"R36","series-title":"Arch Int Pharmacodyn Ther","first-page":"221","article-title":"Effects of mefloquine on Ca2+ uptake and release by dog brain microsomes","volume":"331","author":"Lee","year":"1996"},{"key":"R37","series-title":"J Protozool Res","first-page":"55","article-title":"Fucoidan inhibits the in vitro growth of Babesia bovis","volume":"14","author":"Takabatake","year":"2004"},{"key":"R38","series-title":"Exp Parasitol","first-page":"290","article-title":"Babesia bigemina: in vitro and in vivo effects of curdlan sulfate on the growth of parasites","volume":"90","author":"Igarashi","year":"1998"},{"key":"R39","series-title":"J Protozool 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