Structure-activity relationship studies of antiplasmodial aminomethylthiazoles

Peter Mubanga Cheuka; Diego Gonzalez Cabrera; Tanya Paquet; Kelly Chibale

doi:10.1016/j.bmcl.2014.09.071

Structure-activity relationship studies of antiplasmodial aminomethylthiazoles

Bioorg Med Chem Lett. 2014 Nov 15;24(22):5207-11. doi: 10.1016/j.bmcl.2014.09.071. Epub 2014 Oct 2.

Authors

Peter Mubanga Cheuka¹, Diego Gonzalez Cabrera¹, Tanya Paquet¹, Kelly Chibale²

Affiliations

¹ Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
² Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa; South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa. Electronic address: [email protected].

PMID: 25316314
DOI: 10.1016/j.bmcl.2014.09.071

Abstract

Structure-activity relationship (SAR) studies around a previously reported antimalarial aminomethylthiazole pyrazole carboxamide 1 are reported. Several analogues were synthesised and profiled for in vitro antiplasmodial activity against the drug-sensitive Plasmodium falciparum malaria parasite strain, NF54. Although all the reported analogues exhibited inferior in vitro antiplasmodial activity (IC50 = 0.125-173 μM) relative to compound 1 (IC50 = 0.0203 μM), one analogue, compound 5a, retained submicromolar activity (IC50 = 0.125 μM).

Keywords: Aminomethylthiazoles; Antimalarial drug; Antiplasmodial activity; Structure–activity relationship; Thiazoles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimalarials / chemistry*
Antimalarials / pharmacology*
Mice
Plasmodium falciparum / drug effects*
Plasmodium falciparum / physiology
Structure-Activity Relationship
Thiazoles / chemistry*
Thiazoles / pharmacology*

Substances

Antimalarials
Thiazoles