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@ARTICLE{Rasheed:639284,
author = {Rasheed, Saima and Huda, Noo rul and Warsi, Zoha and Tahir,
Syeda Sarah and Ahmad, Malik Shoaib and Gul, Sadaf and Arif,
Rida and Falke, Sven},
title = {{D}rug repurposing: {I}dentification and {X}-ray
crystallographic analyses of {US}-{FDA} approved drugs
against carbonic anhydrase-{II}},
journal = {International journal of biological macromolecules},
volume = {305},
issn = {0141-8130},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {PUBDB-2025-04385},
pages = {141057},
year = {2025},
note = {Waiting for fulltext},
abstract = {Of all isoforms, human carbonic anhydrase II (PF00194; EC
4.2.1.1), which is mostly found in red cells, kidneys, and
the eyes, plays a pivotal role in numerous physiological
processes, and its dysregulation has been linked to the wide
range of illnesses, such as glaucoma. Finding new inhibitors
that target carbonic anhydrase II, therefore has great
potential in drug discovery. Using drug repurposing
approach, this study focused on the investigation of
different drugs as Carbonic anhydrase II inhibitors and
their structural studies using X-ray crystallography. For
this purpose, 100 different drugs were evaluated for bovine
and human carbonic anhydrase II inhibitory activity. Among
all, two drugs, i.e. acetohexamide (1) and levosulpiride
(54) were found to be active, with IC$_{50}$ = 437.0 ± 0.2
and 1128 ± 0.75 μM, respectively. Mechanistic studies
suggested that both drugs are competitive inhibitors of the
human carbonic anhydrase II enzyme. The X-ray crystal
structure analysis revealed that acetohexamide (1) interacts
via terminal acetyl group with the active site residues of
the carbonic anhydrase II enzyme, and showed strong hydrogen
bonding with Zn, His94, His119, and Asn67. The sulfonamide
group of levosulpiride was involved in strong hydrogen
bonding with Zn, His94, His119, and Thr199. From in vivo
studies, we found that carbonic anhydrase activity was
significantly inhibited by the intraperitoneal
administration of levosulpiride for up to 5 h. Our findings
provide comprehensive insights for the optimization of the
pharmacological profile of these drugs, and provide avenues
for the exploration of different derivatives of these drugs
with enhanced efficacy and fewer adverse effects.},
cin = {FS-CFEL-1-BMX},
ddc = {570},
cid = {I:(DE-H253)FS-CFEL-1-BMX-20210408},
pnm = {633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633)},
pid = {G:(DE-HGF)POF4-633},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
doi = {10.1016/j.ijbiomac.2025.141057},
url = {https://bib-pubdb1.desy.de/record/639284},
}