Tiwari Ghanshyam, Mishra Vinay Kumar, Kumari Priti, Khanna Ashish, Sharma Sunil, Sagar Ram
Department of Chemistry, Institute of Science, Banaras Hindu University Varanasi 221005 India
Glycochemistry Laboratory, School of Physical Sciences, Jawaharlal Nehru University New Delhi 110067 India.
RSC Adv. 2024 Jan 3;14(2):1304-1315. doi: 10.1039/d3ra06993a. eCollection 2024 Jan 2.
In the pursuit of novel therapeutic agents, we present a comprehensive study on the design, synthesis, and evaluation of a diverse library of triazole bridged -glycosides of pyrazolo[1,5-]pyrimidinones, employing a microwave-assisted synthetic approach 'click chemistry'. This methodology offers efficient and accelerated access to the glycohybrids, showcasing improved reaction conditions that yield high-quality products. In this research endeavor, we have successfully synthesized a series of twenty-seven triazole bridged -glycosides of pyrazolo[1,5-]pyrimidinones. Our investigation extends beyond synthetic endeavors to explore the potential therapeutic relevance of these compounds. We subjected them to rigorous screening against prominent breast cancer cell lines MCF-7, MDA-MB231, and MDA-MB453. Among the library of compounds synthesized, (2,3,4,5,6)-2-(acetoxymethyl)-6-(4-((5-(4-methoxyphenyl)-7-oxopyrazolo[1,5-]pyrimidin-1(7)-yl)methyl)-1-1,2,3-triazol-1-yl)tetrahydro-2-pyran-3,4,5-triyl triacetate emerged as a potent compound, exhibiting remarkable anti-cancer activity with an IC value of 27.66 μM against the MDA-MB231 cell line. Additionally, (2,3,4,5,6)-2-(acetoxymethyl)-6-(4-((7-oxo-5-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-]pyrimidin-1(7)-yl)methyl)-1-1,2,3-triazol-1-yl)tetrahydro-2-pyran-3,4,5-triyl triacetate displayed notable inhibitory potential against the MCF-7 cell line, with an IC value of 4.93 μM. Furthermore, docking analysis was performed to validate our experimental findings. These findings underscore the promise of our triazole bridged -glycosides of pyrazolo[1,5-]pyrimidinones as potential anti-cancer agents. This research not only enriches the field of glycohybrid synthesis but also contributes valuable insights into the development of novel anti-cancer therapeutics.
在寻求新型治疗药物的过程中，我们采用微波辅助合成方法“点击化学”，对吡唑并[1,5 - ]嘧啶酮的三唑桥连糖苷类多样文库进行了全面的设计、合成及评估研究。这种方法为获取糖杂合物提供了高效且加速的途径，展示了能产生高质量产物的改进反应条件。在这项研究工作中，我们成功合成了一系列二十七个吡唑并[1,5 - ]嘧啶酮的三唑桥连糖苷。我们的研究不仅局限于合成工作，还探索了这些化合物潜在的治疗相关性。我们针对著名的乳腺癌细胞系MCF - 7、MDA - MB231和MDA - MB453对它们进行了严格筛选。在合成的化合物文库中，(2,3,4,5,6)-2-(乙酰氧基甲基)-6-(4-((5-(4-甲氧基苯基)-7-氧代吡唑并[1,5 - ]嘧啶-1(7)-基)甲基)-1H - 1,2,3 - 三唑-1 - 基)四氢-2 - 吡喃-3,4,5 - 三基三乙酸酯成为一种强效化合物，对MDA - MB231细胞系表现出显著的抗癌活性，IC值为27.66 μM。此外，(2,3,4,5,6)-2-(乙酰氧基甲基)-6-(4-((7-氧代-5-(4-(三氟甲基)phenyl)吡唑并[1,5 - ]嘧啶-1(7)-基)甲基)-1H - 1,2,3 - 三唑-1 - 基)四氢-2 - 吡喃-3,4,5 - 三基三乙酸酯对MCF - 7细胞系显示出显著的抑制潜力，IC值为4.93 μM。此外，还进行了对接分析以验证我们的实验结果。这些发现强调了我们的吡唑并[1,5 - ]嘧啶酮的三唑桥连糖苷作为潜在抗癌药物的前景。这项研究不仅丰富了糖杂合物合成领域，还为新型抗癌治疗药物的开发提供了有价值的见解。
