Green and Efficient Synthetic Protocol for 1,3,5-Triazine Derivatives with Anticancer Potential Against Colorectal Cancer

作者：Julia Chrzan, Anna K. Drabczyk, Izabela Siemińska, Monika Baj‐Krzyworzeka, Katarzyna Ewa Greber, Jolanta Jaśkowska, Damian Kułaga, Krzesimir Ciura · 发表于：Molecules · 年份：2025 · DOI：10.3390/molecules30112437 · 被引用次数：5 · 研究领域：Synthesis and Characterization of Heterocyclic Compounds、Synthesis of Tetrazole Derivatives、Synthesis and biological activity

Colorectal cancer (CRC) remains a major global health challenge, necessitating the development of more effective and environmentally sustainable treatments. This study presents a novel green synthetic protocol for 1,3,5-triazine derivatives with anticancer potential, employing both microwave-assisted and ultrasound-assisted methods. The synthesis was optimized using 4-chloro-N-(2-chlorophenyl)-6-(morpholin-4-yl)-1,3,5-triazin-2-amine as the key intermediate, with sodium carbonate, TBAB, and DMF providing optimal yields under microwave conditions. To enhance sustainability, a modified sonochemical method was also developed, enabling efficient synthesis in aqueous media with a minimal use of organic solvents. A series of nine morpholine-functionalized derivatives were synthesized and evaluated for cytotoxic activity against SW480 and SW620 colorectal cancer cell lines. Compound 11 demonstrated superior antiproliferative activity (IC₅₀ = 5.85 µM) compared to the reference drug 5-fluorouracil, while compound 5 showed promising dual-line activity. In silico ADME analysis supported the drug likeness of the synthesized compounds, and biomimetic chromatography analysis confirmed favorable physicochemical properties, including lipophilicity and membrane affinity. These results underscore the potential of the developed protocol to produce bioactive triazine derivatives through an efficient, scalable, and environmentally friendly process, offering a valuable strategy for future anticanc...