Minor groove binders for DNA as antitypanosomal agents: the veterinary context

Colin J. Suckling, Fraser Scott, Abedawn Khalaf, Kirsten Gillingwater, Liam Morrison, Harry de Koning, Michael Barrett, Federica Giordani

Research output: Contribution to conferencePaper

1 Downloads (Pure)

Abstract

Animal African trypanosomiasis (or nagana) is a wasting livestock disease found in sub-Saharan Africa and caused by protozoan parasites Trypanosoma congolense, T. vivax and T. brucei. Chemotherapy (mostly with the diamidine diminazene aceturate) and chemoprophylaxis (mostly with the phenanthridine isometamidium chloride) are essential for disease control. However, as current treatments lose efficacy due to increased drug resistance, the need for new veterinary trypanocides becomes a high-priority. Trypanosoma spp. are one of the genera of parasites that are susceptible to DNA minor groove binder drugs synthesised at the University of Strathclyde (S-MGBs). All three of the above African species are susceptible to S-MGBs and in addition, the South American species, T. cruzi has been shown to be similarly susceptible. One of the principal challenges to obtaining compounds useful in the field is to achieve activity across the range of infectious species so that characterisation of the infection is not required at diagnosis. Over 100 S-MGBs have been evaluated at the University of Glasgow and the Swiss Tropical Health Institute, Basel, and compounds with development potential have been identified. As an example, S-MGB 234 has been shown to be curative in in vivo models of trypanosome infection in mice. Importantly S-MGB 234 does not show cross resistance with other antitrypanosomal drugs such as diminazine, isometamidium, or ethidium bromide, which is consistent with a different route into the parasite’s cell. S-MGBs that contain alkene links, such as in S-MGB 234, are the most active sub-class of S-MGB and point the way towards structural optimisation.
Original languageEnglish
Number of pages19
DOIs
Publication statusPublished - 1 Nov 2017
Event3rd International Electronic Conference on Medicinal Chemistry -
Duration: 1 Nov 201730 Nov 2017
https://sciforum.net/conference/ecmc-3

Conference

Conference3rd International Electronic Conference on Medicinal Chemistry
Period1/11/1730/11/17
Internet address

Keywords

  • livestock disease
  • disease control
  • minor groove binders
  • DNA

Fingerprint Dive into the research topics of 'Minor groove binders for DNA as antitypanosomal agents: the veterinary context'. Together they form a unique fingerprint.

Cite this