Abdelwahab Ashraf H F, Borik Rita M A, Alamri Abdullah A, Mohamed Hany M, Mostafa Mohamed S, Al-Dies Al-Anood M, Ismail Khatib Sayeed, Elhenawy Ahmed A
Department of Physical Sciences, Chemistry Division, College of Science, Jazan University, P.O Box. 114, Jazan 45142, Kingdom of Saudi Arabia.
Department of Chemistry, Umm Al-Qura University, Al-Qunfudah University College, 21912, Al-Qunfudah, Kingdom of Saudi Arabia.
Anticancer Agents Med Chem. 2025;25(16):1253-1271. doi: 10.2174/0118715206376210250319053528.
Heterocyclic compounds are prevalent in nature and essential to life. The synthesis and application of medium-sized ring heterocyclic compounds have gained prominence. Pyranopyrazole is one such compound that has a significant impact on biological and medicinal chemistry. It has attracted interest in agrochemical research due to its fungicidal, bactericidal, and herbicidal properties. Additionally, it exhibits various biological activities, including anti-inflammatory, analgesic, antidiabetic, antimicrobial, anticancer, and antimalarial effects. Furthermore, it has been explored for its potential in treating SARS-CoV-2.
The study synthesized novel pyranopyrazole compounds and evaluated their anticancer efficacy against certain tumor cell lines (MCF-7, HeLa, and PC-3) and antimicrobial activities as deduced through molecular docking studies.
A one-pot, four-component reaction involving ethyl acetoacetate (1), hydrazine hydrate (2), malononitrile or ethyl cyanoacetate (3a, b), and aromatic aldehydes (4a-c) in an ethanolic/piperidine solution was conducted, yielding pyranopyrazoles (5a-f) in moderate to good yields.
This study involved the synthesis of novel pyranopyrazole derivatives 5a-f and the evaluation of their anticancer and antimicrobial activities. These findings indicate that compound 5f is extremely active. It is more potent than 5-fluorourcail and ofloxacin, and it may also have new modes of action that are worth more research, while compound 5d has the highest antimicrobial activity. Molecular docking studies help us learn more about how these chemicals interact with biological targets like the TGF-βI receptor and the choline-binding domain, both of which play a key role in the growth of cancer.
A series of novel pyranopyrazole derivatives 5a-f were synthesized and analyzed using spectral data. Compound 5f stands out as a lead molecule for more study and improvement due to its low IC50 value and high binding affinity. Based on how stable it is in molecular dynamics (MD) simulations and how its anticancer properties are linked to its binding affinities, it may be a strong TGF-βI receptor inhibitor.
杂环化合物在自然界中普遍存在且对生命至关重要。中等大小环杂环化合物的合成与应用已受到广泛关注。吡喃并吡唑就是这样一种对生物和药物化学有重大影响的化合物。由于其具有杀菌、抑菌和除草特性，它在农用化学研究中引起了人们的兴趣。此外，它还表现出多种生物活性，包括抗炎、镇痛、抗糖尿病、抗菌、抗癌和抗疟疾作用。此外，人们还探索了其在治疗新型冠状病毒肺炎（SARS-CoV-2）方面的潜力。
本研究合成了新型吡喃并吡唑化合物，并通过分子对接研究评估了它们对某些肿瘤细胞系（MCF-7、HeLa和PC-3）的抗癌疗效以及抗菌活性。
在乙醇/哌啶溶液中，使乙酰乙酸乙酯（1）、水合肼（2）、丙二腈或氰基乙酸乙酯（3a、b）与芳香醛（4a - c）进行一锅四组分反应，以中等至良好的产率得到吡喃并吡唑（5a - f）。
本研究涉及新型吡喃并吡唑衍生物5a - f的合成及其抗癌和抗菌活性评估。这些结果表明化合物5f具有极高的活性。它比5-氟尿嘧啶和氧氟沙星更有效，并且可能还具有值得进一步研究的新作用模式，而化合物5d具有最高的抗菌活性。分子对接研究有助于我们更深入了解这些化合物如何与生物靶点（如转化生长因子-βI受体和胆碱结合结构域）相互作用，这两个靶点在癌症生长中都起着关键作用。
合成了一系列新型吡喃并吡唑衍生物5a - f，并利用光谱数据进行了分析。化合物5f因其低半数抑制浓度（IC50）值和高结合亲和力，成为进一步研究和改进的先导分子。基于其在分子动力学（MD）模拟中的稳定性以及其抗癌特性与其结合亲和力的关联，它可能是一种强效的转化生长因子-βI受体抑制剂。
