Search for the active ingredients from a 2-aminothiazole DMSO stock solution with antimalarial activity

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 Pf IspE 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 Pf IspE. 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

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

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

Operator Method for Nonperturbative Calculation of the Thermodynamic Values in Quantum Statistics. Diatomic Molecular Gas

Operator method and cumulant expansion are used for nonperturbative calculation of the partition function and the free energy in quantum statistics. It is shown for Boltzmann diatomic molecular gas with some model intermolecular potentials that the zeroth order approximation of the proposed method interpolates the thermodynamic values with rather good accuracy in the entire range of both the Hamiltonian parameters and temperature. The systematic procedure for calculation of the corrections to the zeroth order approximation is also considered.Comment: 22 pages, 7 Postscript figures, accepted for publication in Journal of Physics

Charge-density-wave instability in the Holstein model with quartic anharmonic phonons

The molecular-crystal model, that describes a one-dimensional electron gas interacting with quartic anharmonic lattice vibrations, offers great potentials in the mapping of a relatively wide range of low-dimensional fermion systems coupled to optical phonons onto quantum liquids with retarded interactions. Following a non-perturbative approach involving non-Gaussian partial functional integrations of lattice degrees of freedom, the exact expression of the phonon-mediated two-electron action for this model is derived. With the help of Hubbard-Stratonovich transformation the charge-density-wave instability is examined in the sequel, with particular emphasis on the effect of the quartic anharmonic phonons on the charge-density-wave transition temperature.Comment: 12 pages, 3 figure

Siderophore production by Bacillus megaterium : effect of growth-phase and cultural conditions

Siderophore production by Bacillus megaterium was detected, in an iron-deficient culture medium, during the exponential growth phase, prior to the sporulation, in the presence of glucose; these results suggested that the onset of siderophore production did not require glucose depletion and was not related with the sporulation. The siderophore production by B. megaterium was affected by the carbon source used. The growth on glycerol promoted the very high siderophore production (1,182 μmol g−1 dry weight biomass); the opposite effect was observed in the presence of mannose (251 μmol g−1 dry weight biomass). The growth in the presence of fructose, galactose, glucose, lactose, maltose or sucrose, originated similar concentrations of siderophore (546–842 μmol g−1 dry weight biomass). Aeration had a positive effect on the production of siderophore. Incubation of B. megaterium under static conditions delayed and reduced the growth and the production of siderophore, compared with the incubation in stirred conditions.The authors thank Porto University/Totta Bank for their financial support through the project "Microbiological production of chelating agents" (Ref: 180). The authors also thank the Fundacao para a Ciencia e a Tecnologia (FCT) through the Portuguese Government for their financial support of this work through the grants Strategic project-LA23/2013-2014 (IBB) and PEST-C/EQB/LA0006/2011 (REQUIMTE). Manuela D. Machado gratefully acknowledges the postdoctoral (SFRH/BPD/72816/2010) grant from FCT

Characterizing RecA-Independent Induction of Shiga toxin2-Encoding Phages by EDTA Treatment

Background: The bacteriophage life cycle has an important role in Shiga toxin (Stx) expression. The induction of Shiga toxin-encoding phages (Stx phages) increases toxin production as a result of replication of the phage genome, and phage lysis of the host cell also provides a means of Stx toxin to exit the cell. Previous studies suggested that prophage induction might also occur in the absence of SOS response, independently of RecA. Methodology/Principal Findings: The influence of EDTA on RecA-independent Stx2 phage induction was assessed, in laboratory lysogens and in EHEC strains carrying Stx2 phages in their genome, by Real-Time PCR. RecA-independent mechanisms described for phage l induction (RcsA and DsrA) were not involved in Stx2 phage induction. In addition, mutations in the pathway for the stress response of the bacterial envelope to EDTA did not contribute to Stx2 phage induction. The effect of EDTA on Stx phage induction is due to its chelating properties, which was also confirmed by the use of citrate, another chelating agent. Our results indicate that EDTA affects Stx2 phage induction by disruption of the bacterial outer membrane due to chelation of Mg 2+. In all the conditions evaluated, the pH value had a decisive role in Stx2 phage induction. Conclusions/Significance: Chelating agents, such as EDTA and citrate, induce Stx phages, which raises concerns due to their frequent use in food and pharmaceutical products. This study contributes to our understanding of the phenomenon o

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

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