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Indole and benzimidazole bichalcophenes: synthesis, DNA binding and antiparasitic activity

Farahat, Abdelbasset A. and Ismail, Mohamed A. and Kumar, Arvind and Wenzler, Tanja and Brun, Reto and Paul, Ananya and Wilson, W. David and Boykin, David W.. (2018) Indole and benzimidazole bichalcophenes: synthesis, DNA binding and antiparasitic activity. European Journal of Medicinal Chemistry, 143. pp. 1590-1596.

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Abstract

A novel series of indole and benzimidazole bichalcophene diamidine derivatives were prepared to study their antimicrobial activity against the tropical parasites causing African sleeping sickness and malaria. The dicyanoindoles needed to synthesize the target diamidines were obtained through Stille coupling reactions while the bis-cyanobenzimidazoles intermediates were made via condensation/cyclization reactions of different aldehydes with 4-cyano-1,2-diaminobenzene. Different amidine synthesis methodologies namely, lithium bis-trimethylsilylamide (LiN[Si(CH3)3]2) and Pinner methods were used to prepare the diamidines. Both types (indole and benzimidazole) derivatives of the new diamidines bind strongly with the DNA minor groove and generally show excellent in vitro antitrypanosomal activity. The diamidino-indole derivatives also showed excellent in vitro antimalarial activity while their benzimidazole counterparts were generally less active. Compound 7c was highly active in vivo and cured all mice infected with Trypanosoma brucei rhodesiense, a model that mimics the acute stage of African sleeping sickness, at a low dose of 4 × 5 mg/kg i.p. and hence 7c is more potent in vivo than pentamidine.
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
Publisher:Elsevier
ISSN:0223-5234
e-ISSN:1768-3254
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:14 Sep 2018 12:30
Deposited On:02 Feb 2018 13:53

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