Chemical decomposition of DMSO stock solutions is a common
incident that can mislead biological screening campaigns. Here,
we share our case study of 2-aminothiazole 1, originating from
an antimalarial class that undergoes chemical decomposition in
DMSO at room temperature. As previously measured biological
activities observed against Plasmodium falciparum NF54 and for
the target enzyme PfIspE were not reproducible for a fresh
batch, we tackled the challenge to understand where the
activity originated from. Solvent- and temperature-dependent
studies using HRMS and NMR spectroscopy to monitor the
decomposition led to the isolation and in vitro evaluation of
several fractions against PfIspE. After four days of decomposition, we successfully isolated the oxygenated and dimerised
compounds using SFC purification and correlated the observed
activities to them. Due to the unstable nature of the two
isolates, it is likely that they undergo further decomposition
contributing to the overall instability of the compound