Potential thiosemicarbazone‐based enzyme inhibitors: Assessment of antiproliferative activity, metabolic enzyme inhibition properties, and molecular docking calculations
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Date
2022/01/26Author
Yakan,HasanKoçyiğit,Ümit M.
Muğlu, Halit
Ergul,Mustafa
Erkan,Sultan
Güzel,Emre
Taslimi, Parham
Gülçin,İlhami
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A new series of thiosemicarbazone derivatives (1–11) were prepared from various
aldehydes and isocyanates with high yields and practical methods. The structures of
these compounds were elucidated by Fourier transform infrared, 1H‐nuclear magnetic
resonance (NMR), 13C‐NMR spectroscopic methods and elemental analysis.
Cytotoxic effects of target compounds were determined by 2,3‐bis‐(2‐methoxy‐4‐
nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide assay and compound 1 showed
significant cytotoxic activity against both MCF‐7 and MDA‐MB‐231 cells, with halfmaximal
inhibitory concentration values of 2.97 μM and 6.57 μM, respectively.
Moreover, in this study, the anticholinergic and antidiabetic potentials of these
compounds were investigated. To this aim, the effect of the newly synthesized
thiosemicarbazone derivatives on the activities of acetylcholinesterase (AChE) and
αglycosidase (α‐Gly) was evaluated spectrophotometrically. The title compounds
demonstrated high inhibitory activities compared to standard inhibitors with Ki values
in the range of 122.15–333.61 nM for α‐Gly (Ki value for standard inhibitor =
75.48 nM), 1.93–12.36 nM for AChE (Ki value for standard inhibitor = 17.45 nM).
Antiproliferative activity and enzyme inhibition at the molecular level were performed
molecular docking studies for thiosemicarbazone derivatives. 1M17, 5FI2,
and 4EY6, 4J5T target proteins with protein data bank identification with (1–11)
compounds were docked for anticancer and enzyme inhibition, respectively.
Source
Journal of Biomolecular Structure and DynamicsVolume
40Issue
2URI
https://www.tandfonline.com/doi/full/10.1080/07391102.2020.1818623https://hdl.handle.net/20.500.12418/13855