% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Jaladanki:892139,
author = {Jaladanki, Chaitanya K. and Khatun, Samima and Gohlke,
Holger and Bharatam, Prasad V.},
title = {{R}eactive {M}etabolites from {T}hiazole-{C}ontaining
{D}rugs: {Q}uantum {C}hemical {I}nsights into
{B}iotransformation and {T}oxicity},
journal = {Chemical research in toxicology},
volume = {34},
number = {6},
issn = {1520-5010},
address = {New York, NY},
publisher = {ACS Publ.},
reportid = {FZJ-2021-01973},
pages = {1503–1517},
year = {2021},
abstract = {Drugs containing thiazole and aminothiazole groups are
known to generate reactive metabolites (RMs) catalyzed by
cytochrome P450s (CYPs). These RMs can covalently modify
essential cellular macromolecules and lead to toxicity and
induce idiosyncratic adverse drug reactions. Molecular
docking and quantum chemical hybrid DFT study were carried
out to explore the molecular mechanisms involved in the
biotransformation of thiazole (TZ) and aminothiazole (ATZ)
groups leading to RM epoxide, S-oxide, N-oxide, and
oxaziridine. The energy barrier required for the epoxidation
is 13.63 kcal/mol, that is lower than that of S-oxidation,
N-oxidation, and oxaziridine formation (14.56, 17.90, and
20.20, kcal/mol respectively). The presence of the amino
group in ATZ further facilitates all the metabolic pathways,
for example, the barrier for the epoxidation reaction is
reduced by ∼2.5 kcal/mol. Some of the RMs/their isomers
are highly electrophilic and tend to form covalent bonds
with nucleophilic amino acids, finally leading to the
formation of metabolic intermediate complexes (MICs). The
energy profiles of these competitive pathways have also been
explored},
cin = {JSC / NIC / IBI-7 / IBG-4},
ddc = {610},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
I:(DE-Juel1)IBI-7-20200312 / I:(DE-Juel1)IBG-4-20200403},
pnm = {217 - Für eine nachhaltige Bio-Ökonomie – von
Ressourcen zu Produkten (POF4-217) / 5111 - Domain-Specific
Simulation $\&$ Data Life Cycle Labs (SDLs) and Research
Groups (POF4-511) / Forschergruppe Gohlke $(hkf7_20200501)$},
pid = {G:(DE-HGF)POF4-217 / G:(DE-HGF)POF4-5111 /
$G:(DE-Juel1)hkf7_20200501$},
typ = {PUB:(DE-HGF)16},
pubmed = {33900062},
UT = {WOS:000664624800013},
doi = {10.1021/acs.chemrestox.0c00450},
url = {https://juser.fz-juelich.de/record/892139},
}