Potential thiosemicarbazone‐based enzyme inhibitors: Assessment of antiproliferative activity, metabolic enzyme inhibition properties, and molecular docking calculations

Abstract

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 half‐maximal 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.

Cucurbitacin I exhibits anticancer efficacy through induction of apoptosis and modulation of JAK / STAT3 , MAPK / ERK , and AKT / mTOR signaling pathways in HepG2 cell line

“…The antiproliferation of malignant cells is mediated by molecules involved in cell cycle regulation, which suppress uncontrolled cell proliferation (Altay et al, 2019; Yakan et al, 2022). Molecular studies have shown that CuI halts the cell cycle via Aurora kinases, which play a role in the mitosis stage of the cell cycle.…”

“…For example, mTOR inhibitors have been reported to prevent tumor development by significantly reducing the proliferative activity of HCC cells and increasing the apoptotic effect (Semela et al, 2007;Sieghart et al, 2007). Preclinical studies on some of the mTOR inhibitors in HCC models are continuing (Zhu et al, 2014). Furthermore, studies have shown abnormally activated MAPK cascade in HCC with HBV infection (Diniz et al, 2020).…”

“…Moreover, the present study also investigated the effect of CuI on DNA fragmentation in HepG2 cells with the alkaline Comet assay. The DNA fragmentation analyses showed that CuI increased the rate of DNA damage in a dosedependent manner (Figure10).The antiproliferation of malignant cells is mediated by molecules involved in cell cycle regulation, which suppress uncontrolled cell proliferation(Altay et al, 2019;Yakan et al, 2022). Molecularstudies have shown that CuI halts the cell cycle via Aurora kinases, which play a role in the mitosis stage of the cell cycle.…”

Arylated Quinoline and Tetrahydroquinolines: Synthesis, Characterization and Their Metabolic Enzyme Inhibitory and Antimicrobial Activities

“…[40] Inhibitor IC 50 values have been determined using the following studies: The activities of thiosemicarbazone derivatives were tested at various inhibitor concentrations, and graphs (Figure 1) were constructed as percent activity -[I], with IC 50 values determined from the equation of the curve. [41]…”

Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4‐hydroxy‐3,5‐dimethoxy benzaldehyde motif

“…In this study, new thiosemicarbazones bearing Schiff-bases (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) were accomplished by condensation reaction with 4-hydroxy-3, 5-dimethoxy benzaldehyde and various isocyanates under reflux in ethanol. The structures of the compounds were characterized by Fourier transform infrared (FT-IR), proton-carbon nuclear magnetic resonance ( 1 H NMR, 13 C NMR), and ultraviolet-visible (UV-Vis) spectroscopic methods and elemental analysis.…”