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

Suckling, Colin J. and Scott, Fraser and Khalaf, Abedawn and Gillingwater, Kirsten and Morrison, Liam and de Koning, Harry and Barrett, Michael and Giordani, Federica (2017) Minor groove binders for DNA as antitypanosomal agents : the veterinary context. In: 3rd International Electronic Conference on Medicinal Chemistry, 2017-11-01 - 2017-11-30. (https://doi.org/10.3390/ecmc-3-04647)

[thumbnail of Suckling-etal-IECMC-2017-Minor-groove-binders-for-DNA-as-antitypanosomal-agents]
Preview
 Text. Filename: Suckling_etal_IECMC_2017_Minor_groove_binders_for_DNA_as_antitypanosomal_agents.pdf
Final Published Version
Download (1MB)| Preview

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.

ORCID iDs

Suckling, Colin J., Scott, Fraser ORCID logoORCID: https://orcid.org/0000-0003-0229-3698, Khalaf, Abedawn ORCID logoORCID: https://orcid.org/0000-0001-9162-7527, Gillingwater, Kirsten, Morrison, Liam, de Koning, Harry, Barrett, Michael and Giordani, Federica;
  • Item type:Conference or Workshop Item(Paper)
    ID code:69473
    Dates:
    Date
    Event
    1 November 2017
    Published
    20 October 2017
    Accepted
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:22 Aug 2019 14:40
    Last modified:13 Nov 2024 01:35
    URI:https://strathprints.strath.ac.uk/id/eprint/69473
CORE (COnnecting REpositories)