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Exploration of larger central ring linkers in furamidine analogues : synthesis and evaluation of their DNA binding, antiparasitic and fluorescence properties

Farahat, A. A. and Paliakov, E. and Kumar, A. and Barghash, A. E. and Goda, F. E. and Eisa, H. M. and Wenzler, T. and Brun, R. and Liu, Y. and Wilson, W. D. and Boykin, D. W.. (2011) Exploration of larger central ring linkers in furamidine analogues : synthesis and evaluation of their DNA binding, antiparasitic and fluorescence properties. Bioorganic & medicinal chemistry : a Tetrahedron publication for the rapid dissemenination of full original research papers and critical reviews on biomolecular chemistry, medicinal chemistry and related disciplines, 19 (7). pp. 2156-2167.

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Official URL: http://edoc.unibas.ch/dok/A6002194

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Abstract

The effects of replacing the central furan ring of furamidine with indole and benzimidazole on their DNA binding affinity, antiparasitic activity and fluorescence are reported. The bis-cyanophenylindoles required to make the corresponding amidines were prepared by sequential Stille and/or Suzuki coupling reactions. The bis-cyanophenylbenzimidazoles were obtained by coupling 4-cyanobenzaldehydes with the appropriate cyano substituted phenylenediamine. The bis-nitriles were converted to the diamidines by reaction with LiN[Si(CH(3))(3)](2) or by Pinner methodology. Specifically, we have prepared new series of 2,6- and 2,5-diaryl indoles (6a,b, 12 and 17a-d) and the related benzimidazoles (24, 30 and 35). The new compounds bind in the DNA minor groove in DNA AT base pair sequences and eight of the ten new analogues exhibit DeltaT(m) values comparable to or higher than that of furamidine. Six of ten of the new compounds exhibit lower IC(50) values against Trypanosoma brucei rhodesiense (T. b. r.) and eight of ten exhibit lower IC(50) values against Plasmodium falciparum (P. f.) than furamidine. Four of the ten show greater efficacy than furamidine in the rigorous T. b. r. STIB900 mouse model for African trypanosomiasis. Generally, the fluorescence properties of the new analogues are similar to that of DAPI
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Brun, Reto and Wenzler, Tanja
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Pergamon
ISSN:0968-0896
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Nov 2017 08:30
Deposited On:08 Nov 2012 16:21

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