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Synthesis and antiprotozoal activities of benzyl phenyl ether diamidine derivatives

Patrick, Donald A. and Bakunov, Stanislav A. and Bakunova, Svetlana M. and Jones, Susan Kilgore and Wenzler, Tanja and Barszcz, Todd and Kumar, Arvind and Boykin, David W. and Werbovetz, Karl A. and Brun, Reto and Tidwell, Richard R.. (2013) Synthesis and antiprotozoal activities of benzyl phenyl ether diamidine derivatives. European journal of medicinal chemistry, 67. pp. 310-324.

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Official URL: http://edoc.unibas.ch/dok/A6174418

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Abstract

Sixty-two cationic benzyl phenyl ether derivatives (36 amidines and 26 prodrugs) were prepared and assayed for activities in vitro and in vivo against Trypanosoma brucei rhodesiense (STIB900), and in vitro against Plasmodium falciparum (K1) and Leishmania donovani axenic amastigotes. 3-Amidinobenzyl 4-amidino-2-iodo-6-methoxyphenyl ether dihydrochloride (55, IC50 = 3.0 nM) and seven other compounds exhibited IC50 values below 10 nM against T. b. rhodesiense in vitro. The 2-bromo-4,4'-diamidino analogue 19 (IC50 = 4.0 nM) and 12 other analogues were more potent than pentamidine (IC50 = 46 nM) against P. falciparum. The 3',4-diamidino-2,6-diiodo analogue 49 (IC50 = 1.4 μM) and two other compounds were more effective than pentamidine (IC50 = 1.8 μM) against L. donovani. A prodrug, 3',4-bis(N″-methoxy)amidino-2-bromo derivative 38, was the most efficacious against trypanosome infected mice, attaining 4/4 cures in four daily 25 mg/kg oral doses, and the 2-chloro-4,4'-diamidine 18 cured 3/4 mice in four daily 5 mg/kg intraperitoneal doses.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Wenzler, Tanja and Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:EDIFOR
ISSN:0223-5234
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Sep 2018 14:30
Deposited On:25 Oct 2013 08:33

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