5-methyl-N'-(thiophen-2-ylmethylene)-1H-pyrazole-3-carbohydrazide as potent anticancer agent: Synthesis, spectroscopic characterization, anticancer activity and DFT studies

IF 4 2区 化学 Q2 CHEMISTRY, PHYSICAL
Issam Ameziane El Hassani , Silvia A. Brandán , Ahmet Altay , Esma Yeniçeri , Ali Alsalme , Afaf Oulmidi , M'hammed Ansar , Khalid Karrouchi
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引用次数: 0

Abstract

A new pyrazole-hydrazide hydrazone derivative, named 5-methyl-N'-(thiophen-2-ylmethylene)-1H-pyrazole-3-carbohydrazide (TMPC) has been synthesized and characterized by FT-IR, UV–Vis, 1H NMR, 13C NMR, and HRMS-ESI. Its cytotoxic activity was tested on various cancer and healthy cell lines using the XTT method. In addition, the advanced anticancer mechanism was investigated by flow cytometry analysis. Hybrid B3LYP/6–311++G** calculations reveal two stable C1 and C2 conformers of TMPC with energy differences of 28.96 kJ/mol in the gas phase and 8.50 kJ/mol in ethanol solution. Comparisons among the experimental NMR, UV and infrared spectra with the predicted ones support the presence of both forms in solution. The presence of dimer C2 justify the intensities and numerous bands observed in the IR spectrum in the 2000–10 cm−1 region. Probably, the repulsion between the N7 and O1 atoms in C1 explain its lower stability and the higher solvation energy (-108.20 kJ/mol) observed for this form in ethanol than C2 (-88.01 kJ/mol). NBO calculations suggest that both forms are stable in the two media while the AIM analyses evidence the higher stability of C2 than C1 due to the N9-H22···N7 interaction observed only for this conformer in the gas phase. Gap values suggest high reactivities of both forms, as compared with similar pyrazole-carbohydrazide species. Full vibrational assignments are reported for both forms of TMPC together with the main scaled force constants. The XTT results showed that TMPC exhibited a selective cytotoxic effect on the tested cancer cell lines in a dose- and time-dependent manner, and also displayed the most potent cytotoxic activity against breast cancer MCF-7 cells with an IC50 value of 22.79 µM after 48 h Flow cytometric analyses showed that TMPC induced apoptosis and suppressed PI3K/Akt signaling in MCF-7 cells.

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来源期刊
Journal of Molecular Structure
Journal of Molecular Structure 化学-物理化学
CiteScore
7.10
自引率
15.80%
发文量
2384
审稿时长
45 days
期刊介绍: The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.
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