TY  - JOUR
A1  - Geroldinger, Gerald
A1  - Tonner, Matthias
A1  - Fudickar, Werner
A1  - De Sarkar, Sritama
A1  - Dighal, Aishwarya
A1  - Monzote, Lianet
A1  - Staniek, Katrin
A1  - Linker, Torsten
A1  - Chatterjee, Mitali
A1  - Gille, Lars
T1  - Activation of anthracene endoperoxides in leishmania and impairment of mitochondrial functions
JF  - Molecules
N2  - Leishmaniasis is a vector-borne disease caused by protozoal Leishmania. Because of resistance development against current drugs, new antileishmanial compounds are urgently needed. Endoperoxides (EPs) are successfully used in malaria therapy, and experimental evidence of their potential against leishmaniasis exists. Anthracene endoperoxides (AcEPs) have so far been only technically used and not explored for their leishmanicidal potential. This study verified the in vitro efficiency and mechanism of AcEPs against both Leishmania promastigotes and axenic amastigotes (L. tarentolae and L. donovani) as well as their toxicity in J774 macrophages. Additionally, the kinetics and radical products of AcEPs’ reaction with iron, the formation of radicals by AcEPs in Leishmania, as well as the resulting impairment of parasite mitochondrial functions were studied. Using electron paramagnetic resonance combined with spin trapping, photometry, and fluorescence-based oximetry, AcEPs were demonstrated to (i) show antileishmanial activity in vitro at IC50 values in a low micromolar range, (ii) exhibit host cell toxicity in J774 macrophages, (iii) react rapidly with iron (II) resulting in the formation of oxygen- and carbon-centered radicals, (iv) produce carbon-centered radicals which could secondarily trigger superoxide radical formation in Leishmania, and (v) impair mitochondrial functions in Leishmania during parasite killing. Overall, the data of different AcEPs demonstrate that their structures besides the peroxo bridge strongly influence their activity and mechanism of their antileishmanial action.
KW  - Leishmania
KW  - endoperoxides
KW  - EPR spectroscopy
KW  - mitochondria
KW  - radicals
Y1  - 2018
U6  - https://doi.org/10.3390/molecules23071680
SN  - 1420-3049
VL  - 23
IS  - 7
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Linker, Torsten
T1  - Addition of Heteroatom Radicals to endo-Glycals
JF  - Chemistry
N2  - Radical reactions have found many applications in carbohydrate chemistry, especially in the construction of carbon–carbon bonds. The formation of carbon–heteroatom bonds has been less intensively studied. This mini-review will summarize the efforts to add heteroatom radicals to unsaturated carbohydrates like endo-glycals. Starting from early examples, developed more than 50 years ago, the importance of such reactions for carbohydrate chemistry and recent applications will be discussed. After a short introduction, the mini-review is divided in sub-chapters according to the heteroatoms halogen, nitrogen, phosphorus, and sulfur. The mechanisms of radical generation by chemical or photochemical processes and the subsequent reactions of the radicals at the 1-position will be discussed. This mini-review cannot cover all aspects of heteroatom-centered radicals in carbohydrate chemistry, but should provide an overview of the various strategies and future perspectives
KW  - radicals
KW  - carbohydrates
KW  - heteroatoms
KW  - synthesis
Y1  - 2020
U6  - https://doi.org/10.3390/chemistry2010008
SN  - 2624-8549
VL  - 2
IS  - 1
SP  - 80
EP  - 92
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Bauch, Marcel
A1  - Klaper, Matthias
A1  - Linker, Torsten
T1  - Intermediates in the cleavage of endoperoxides
JF  - Journal of physical organic chemistry
N2  - The decomposition of anthracene endoperoxides has been investigated under various conditions. Thermolyses proceed via radical intermediates and afford anthracenes and rearrangement products, depending on the substitution pattern. Interestingly, not only the O-O but also the C-O bond can be cleaved homolytically. Under basic conditions fragmentations take place, affording anthraquinone, and reactive oxygen species. This mechanism explains the often observed decomposition of endoperoxides during work-up. Finally, an acid-catalyzed cleavage has been observed under release of hydrogen peroxide. The results should be interesting for the mechanistic understanding of peroxide decomposition and the endoperoxides might serve as mild sources of reactive oxygen species for future applications. Copyright (C) 2016 John Wiley & Sons, Ltd.
KW  - peroxides
KW  - radicals
KW  - reaction mechanism
KW  - reactive intermediates
Y1  - 2017
U6  - https://doi.org/10.1002/poc.3607
SN  - 0894-3230
SN  - 1099-1395
VL  - 30
PB  - Wiley
CY  - Hoboken
ER  -