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Antiprotozoal activity and DNA binding of N-substituted N-phenylbenzamide and 1,3-diphenylurea bisguanidines

Ríos Martínez, Carlos H. and Lagartera, Laura and Kaiser, Marcel and Dardonville, Christophe. (2014) Antiprotozoal activity and DNA binding of N-substituted N-phenylbenzamide and 1,3-diphenylurea bisguanidines. European journal of medicinal chemistry, 81. pp. 481-491.

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Official URL: http://edoc.unibas.ch/dok/A6298953

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Abstract

Two series of N-alkyl, N-alkoxy, and N-hydroxy bisguanidines derived from the N-phenylbenzamide and 1,3-diphenylurea scaffolds were synthesised in three steps from the corresponding 4-amino-N-(4-aminophenyl)benzamide and 1,3-bis(4-aminophenyl)urea, respectively. All of the new compounds were evaluated in vitro against T. b. rhodesiense (STIB900) trypomastigotes and Plasmodium falciparum NF54 parasites (erythrocytic stage). N-alkoxy and N-hydroxy derivatives showed weak micromolar range IC50 values against T. b. rhodesiense and P. falciparum whereas the N-alkyl analogues displayed submicromolar and low nanomolar IC50 values against P. falciparum and Trypanosoma brucei, respectively. Two compounds, 4-(2-ethylguanidino)-N-(4-(2-ethylguanidino)phenyl)benzamide dihydrochloride (7b) and 4-(2-isopropylguanidino)-N-(4-(2-isopropylguanidino)phenyl)benzamide dihydrochloride (7c), which showed favourable drug-like properties and in vivo efficacy (100% cures) in the STIB900 mouse model of acute human African trypanosomiasis represent interesting leads for further in vivo studies. The binding of these compounds to AT-rich DNA was confirmed by surface plasmon resonance (SPR) biosensor experiments.
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 (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0223-5234
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Dec 2017 10:39
Deposited On:10 Oct 2014 09:19

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