Synthesis, DNA binding and antitrypanosomal activity of benzimidazole analogues of DAPI

  • Bioorg Med Chem Lett. 2016 Dec 15;26(24):5907-5910. doi: 10.1016/j.bmcl.2016.11.006.
Abdelbasset A Farahat  1 ,  Cheree Bennett-Vaughn  2 ,  Ekaterina M Mineva  2 ,  Arvind Kumar  2 ,  Tanja Wenzler  3 ,  Reto Brun  3 ,  Yang Liu  2 ,  W David Wilson  2 ,  David W Boykin  2
Affiliations
  • 1. Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: [email protected].
  • 2. Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
  • 3. Swiss Tropical and Public Health Institute, Basel 4002, Switzerland; University of Basel, Basel 4003, Switzerland.
PMID: 27843114 DOI: 10.1016/j.bmcl.2016.11.006
Abstract

A series of novel benzimidazole diamidines were prepared from the corresponding dicyano analogues either by applying Pinner methodology (5a-c, 10 and 13a) or by making amidoximes intermediates that were reduced to the corresponding amidines (15a-c). The new amidines were evaluated in vitro against the protozoan parasite Trypanosoma brucei rhodesiense (T. b. r.). The thiophene analogue 5b and the N-methyl compound 15a showed superior antitrypanosomal activity compared to that of the parent I.

Keywords
Antitrypanosomal activity; Benzimidazole diamidines; DAPI; DNA minor groove binders.