The antimalarial activity of 4-aminoalcohol quinoline enantiomers

Abstract

Introduction: Plasmodium falciparum is a deadly parasite that has developed resistance to existing drugs. 4-Amino-alcohols (4-AQ) are potent antimalarial drugs (e.g. chloroquine, mefloquine and quinine) that block the process of transforming heam to heamozoin in the digestive vacuole of the parasite. Objectives: Given four derivatives of 4-AQ the question addressed was what aspect of the molecule enhances its antimalarial activity in Dd2 chloroquine-resistant parasites? Materials and methods: To determine the activity of four derivatives of 4-AQ by measuring their ‘ IC50’ (i.e. dose required to inhibit growth of the parasite by 50%) using a SYBR Green I malaria drug sensitivity assay. Results: The five-carbon derivative was found to be more effective than the seven-carbon derivative. Furthermore, (R )-enantiomers were found to be less active than their (S )-enantiomer counterparts. Conclusions: Data from this study provides a hypothetical model for amino alcohol uptake, action and proposed resistance in P. falciparum . Acknowledgements: Dr Paul Horrocks (Keele University) for use of his laboratory, Mr Imran Ullah (Keele University) for supervising and helping us with this project, Catherin Mullie for providing drug samples and Dr Waleed Alshaqha for supporting us in our project trip.