Synthesis of triazole bridged -glycosides of pyrazolo[1,5-]pyrimidinones as anticancer agents and their docking studies.

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.