Search for the Active Ingredients from a 2-Aminothiazole DMSO Stock Solution with Antimalarial Activity.

Autor: Ropponen HK; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany., Bader CD; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany., Diamanti E; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany.; Helmholtz International Lab for Anti-Infectives, Campus E8.1, 66123, Saarbrücken, Germany., Illarionov B; Hamburg School of Food Science, University of Hamburg, Grindelallee 117, 20146, Hamburg, Germany., Rottmann M; Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.; Universität Basel, Petersplatz 1, 4003, Basel, Switzerland., Fischer M; Hamburg School of Food Science, University of Hamburg, Grindelallee 117, 20146, Hamburg, Germany., Witschel M; BASF-SE, Carl-Bosch-Strasse 38, 67056, Ludwigshafen, Germany., Müller R; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany.; Helmholtz International Lab for Anti-Infectives, Campus E8.1, 66123, Saarbrücken, Germany., Hirsch AKH; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Centre for Infection Research (HZI), Campus E8.1, 66123, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, Campus E8.1, 66123, Saarbrücken, Germany.; Helmholtz International Lab for Anti-Infectives, Campus E8.1, 66123, Saarbrücken, Germany.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2021 Jul 06; Vol. 16 (13), pp. 2089-2093. Date of Electronic Publication: 2021 May 07.
DOI: 10.1002/cmdc.202100067
Abstrakt: 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.
(© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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