Semicarbazone, thiosemicarbazone tailed isoxazoline-pyrazole: synthesis, DFT, biological and computational assessment.

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2024-09-18 DOI:10.1080/17568919.2024.2394011

Abdoullah Bimoussa,Mouhi Eddine Hachim,Khalil El Khatabi,Yassine Laamari,Ali Oubella,Mohamed F AlAjmi,Aziz Auhmani,Mohammed Aziz Ajana,Hamid Morjani,My Youssef Ait Itto

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引用次数: 0

Abstract

Aim: A series of semicarbazone and thiosemicarbazone-tailed hybrids comprising pyrazole and acetylisoxazoline were prepared from (R)-carvone and characterized by technique spectroscopies Nuclear Magnetic Resonance (NMR), IR and High-Resolution Mass Spectrometry. Density Functional Theory (DFT) determined the structural parameters. Their cytotoxic activity was evaluated in vitro against four human cancer cell lines.Methods & results: All the studied semi and thiosemicarbazone demonstrate a promising potential as anticancer agents. The mechanism of action of these compounds involves apoptosis in HT-1080 cells, supported by an increase in the level of caspase-3/7 activity, which also arrests the cell cycle in the G0/G1 phase. Molecular docking studies were performed to establish the potential of the most active compounds 4a and 5a. ADMET analysis showed appropriate pharmacokinetic properties, allowing structure prediction for anticancer activity.

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半咔唑酮、硫代咔唑酮尾部异噁唑啉-吡唑：合成、DFT、生物学和计算评估。

目的：以(R)-香芹酮为原料，制备了一系列由吡唑和乙酰异噁唑啉组成的半咔唑酮和硫代咔唑酮尾杂合体，并利用核磁共振（NMR）、红外光谱和高分辨质谱技术对其进行了表征。密度泛函理论（DFT）确定了结构参数。在体外评估了它们对四种人类癌细胞株的细胞毒性活性：所有研究的半缩酮和硫代氨基脲都显示出作为抗癌剂的巨大潜力。这些化合物的作用机制涉及 HT-1080 细胞的凋亡，其支持因素是 Caspase-3/7 活性水平的提高，这也使细胞周期停滞在 G0/G1 阶段。为了确定活性最强的化合物 4a 和 5a 的潜力，我们进行了分子对接研究。ADMET 分析显示了适当的药代动力学特性，从而可以对抗癌活性进行结构预测。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.