An evaluation of Minor Groove Binders as anti-Trypanosoma brucei brucei therapeutics

Fraser J Scott; Abedawn I Khalaf; Federica Giordani; Pui Ee Wong; Sandra Duffy; Michael Barrett; Vicky M Avery; Colin J Suckling

doi:10.1016/j.ejmech.2016.03.064

An evaluation of Minor Groove Binders as anti-Trypanosoma brucei brucei therapeutics

Eur J Med Chem. 2016 Jun 30:116:116-125. doi: 10.1016/j.ejmech.2016.03.064. Epub 2016 Mar 29.

Authors

Fraser J Scott¹, Abedawn I Khalaf², Federica Giordani³, Pui Ee Wong³, Sandra Duffy⁴, Michael Barrett³, Vicky M Avery⁴, Colin J Suckling²

Affiliations

¹ WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom. Electronic address: [email protected].
² WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
³ Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, United Kingdom.
⁴ Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.

Abstract

A series of 32 structurally diverse MGBs, derived from the natural product distamycin, was evaluated for activity against Trypanosoma brucei brucei. Four compounds have been found to possess significant activity, in the nanomolar range, and represent hits for further optimisation towards novel treatments for Human and Animal African Trypanosomiases. Moreover, SAR indicates that the head group linking moiety is a significant modulator of biological activity.

Keywords: African trypanosomiasis; Antiparasitic activity; Minor Groove Binders.

MeSH terms

Computer Simulation
HEK293 Cells
Humans
Inhibitory Concentration 50
Structure-Activity Relationship
Trypanocidal Agents / chemistry*
Trypanocidal Agents / pharmacology*
Trypanocidal Agents / toxicity
Trypanosoma brucei brucei / drug effects*

Substances

Trypanocidal Agents