Potential thiosemicarbazone-based enzyme inhibitors: assessment of antiproliferative activity, metabolic enzyme inhibition properties, and molecular docking calculations
Yükleniyor...
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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, 1 H-nuclear magnetic resonance (NMR), 13 C-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 half-maximal inhibitory concentration values of 2.97 ?M and 6.57 ?M, 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 ?glycosidase (?-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 ?-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.
Açıklama
Anahtar Kelimeler
Schiff Base, Antiproliferative Activity, Enzyme Inhibition, Molecular Docking, Thiosemicarbazone
Kaynak
J Biochem Mol Toxicol
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
Sayı
Künye
Yakan H, Koçyiğit ÜM, Muğlu H, Ergul M, Erkan S, Güzel E, Taslimi P, Gülçin İ. Potential thiosemicarbazone-based enzyme inhibitors: Assessment of antiproliferative activity, metabolic enzyme inhibition properties, and molecular docking calculations. J Biochem Mol Toxicol. 2022 Feb 24:e23018.
