Computing and Library Services - delivering an inspiring information environment

Selective anti-malarial minor groove binders

Scott, Fraser J., Khalaf, Abedawn I., Duffy, Sandra, Avery, Vicky M. and Suckling, Colin J. (2016) Selective anti-malarial minor groove binders. Bioorganic & Medicinal Chemistry Letters, 26 (14). pp. 3326-3329. ISSN 0960-894X

PDF - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (484kB) | Preview


A set of 31 DNA minor groove binders (MGBs) with diverse structural features relating to both physical chemical properties and DNA binding sequence preference has been evaluated as potential drugs to treat Plasmodium falciparum infections using a chloroquine sensitive strain (3D7) and a chloroquine resistant strain (Dd2) in comparison with human embryonic kidney (HEK) cells as an indicator of mammalian cell toxicity. MGBs with an alkene link between the two N-terminal building blocks were demonstrated to be most active with IC50 values in the range 30–500 nM and therapeutic ratios in the range 10–>500. Many active compounds contained a C-alkylthiazole building block. Active compounds with log D7.4 values of approximately 3 or 7 were identified. Importantly the MGBs tested were essentially equally effective against both chloroquine sensitive and resistant strains. The results show that suitably designed MGBs have the potential for development into clinical candidates for antimalarial drugs effective against resistant strains of Plasmodia.

Item Type: Article
Subjects: Q Science > QD Chemistry
Schools: School of Applied Sciences
Depositing User: Fraser Scott
Date Deposited: 31 Aug 2017 09:25
Last Modified: 28 Aug 2021 15:43


Downloads per month over past year

Repository Staff Only: item control page

View Item View Item

University of Huddersfield, Queensgate, Huddersfield, HD1 3DH Copyright and Disclaimer All rights reserved ©