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

Area of Science:

• Medicinal Chemistry
• Green Chemistry
• Organic Synthesis

Background:

• Colorectal cancer (CRC) presents a significant global health burden, driving the need for innovative and sustainable therapeutic strategies.
• Current treatments face challenges in efficacy and environmental impact, highlighting the demand for novel drug development approaches.

Purpose of the Study:

• To develop a novel, green synthetic protocol for 1,3,5-triazine derivatives with potential anticancer activity.
• To synthesize and evaluate a series of morpholine-functionalized triazine compounds against colorectal cancer cell lines.

Main Methods:

• Microwave-assisted and ultrasound-assisted green synthesis of 1,3,5-triazine derivatives.
• Optimization of synthesis using 4-chloro-N-(2-chlorophenyl)-6-(morpholin-4-yl)-1,3,5-triazin-2-amine intermediate.
• Evaluation of cytotoxic activity against SW480 and SW620 colorectal cancer cell lines.
• In silico ADME analysis and biomimetic chromatography for property assessment.

Main Results:

• A series of nine morpholine-functionalized triazine derivatives were successfully synthesized.
• Compound 11 exhibited potent antiproliferative activity (IC50 = 5.85 µM) against colorectal cancer cells, outperforming 5-fluorouracil.
• Compound 5 demonstrated promising dual-line activity, and in silico/chromatographic analyses confirmed favorable drug-like properties.

Conclusions:

• The developed green synthetic protocol is efficient, scalable, and environmentally friendly for producing bioactive triazine derivatives.
• The synthesized compounds, particularly compound 11, show significant potential for future colorectal cancer drug development.
• This study offers a valuable strategy for advancing sustainable anticancer therapeutics.