Comparison between conventional, grinding, and microwave synthesis of methylpyrazoles as VEGFR-2/HSP90 dual inhibitors.

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-03-31 DOI:10.1080/17568919.2025.2485866

Ebtehal M Husseiny, Rana M Abdelnaby, Najla Altwaijry, Asmaa Saleh, Kurls E Anwer

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引用次数: 0

Abstract

Aim: Embracing structure extension and substitution variation, methylpyrazolones 2-6 and dimethylpyrazoles 8-14 were synthesized as VEGFR-2/HSP90 dual inhibitors.

Materials and methods: The eco-friendly synthesis of the desired analogs was performed by conventional, grinding, and microwave-assisted methods.

Results: All entities have been tested for their antitumor action against three carcinomas, whereas compounds 6, 12, and 13 showed significant cytotoxicity and selectivity toward the examined carcinomas. The consecutive molecular mechanistic studies proved that 6 and 12 exhibited dual inhibition of VEGFR-2 and HSP90 and prompted MCF-7 cycle arrest at G2/M phase followed by apoptosis stimulation.

Conclusion: Molecular docking revealed strong interaction between the potent analogs and VEGFR-2/HSP90 active sites inspiring these congeners to be potential drug candidates in cancer treatment.

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传统、研磨和微波合成甲基吡唑作为VEGFR-2/HSP90双抑制剂的比较

目的：通过结构扩展和取代变化，合成甲基吡唑酮2-6和二甲基吡唑8-14作为VEGFR-2/HSP90双抑制剂。材料和方法：通过常规、研磨和微波辅助的方法对所需的类似物进行了生态友好的合成。结果：化合物6、12、13对三种肿瘤均有明显的细胞毒性和选择性。连续的分子机制研究证明，6和12表现出VEGFR-2和HSP90的双重抑制作用，并在G2/M期引起MCF-7周期阻滞，随后发生凋亡刺激。结论：分子对接揭示了强效类似物与VEGFR-2/HSP90活性位点之间的强相互作用，激发了这些同源物成为癌症治疗的潜在候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.