Canh Pham Em, Thi Le Bich-Ngoc, Ngo Anh Minh, Vong Long Binh, Truong Tuyen Ngoc
Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City 700000 Ho Chi Minh City Vietnam
Faculty of Pharmacy, Hong Bang International University 700000 Ho Chi Minh City Vietnam.
RSC Adv. 2025 Apr 1;15(13):9968-9984. doi: 10.1039/d4ra08508f. eCollection 2025 Mar 28.
A series of symmetrical tri-substituted -triazine derivatives were designed and synthesized by two different methods (reflux and microwave-assisted methods). The structures of compounds were determined by infrared (IR), nuclear magnetic resonance (H NMR and C NMR), and mass spectrometry. The yield of the microwave-assisted method (91-98%) was significantly higher (about 10%) than that of the reflux method (80-88%) meanwhile the reaction time was significantly shorter (15-30 min). Compound 3b showed good cytotoxic activity against the MCF7 (human breast cancer) cell line with an IC value of 6.19 μM. Compounds 3a and 2e showed strong cytotoxic activity against the C26 (colon carcinoma) cell line with IC values of 1.21 and 8.28 μM, respectively. Compound 3e showed good cytotoxic activity against both MCF7 and C26 cell lines with IC values of 13.74, and 14.66 μM respectively. In particular, compound 2d exhibited the best potent cytotoxic activity among the synthesized compounds against both MCF7 and C26 cell lines with IC values of 6.54 and 0.38 μM, respectively. Moreover, compounds 2e, 3a, and 3e showed higher selectivity on cancer cell lines and lower toxicity on BAEC (bovine aorta endothelial) normal cells compared to compounds 2d, 3a, paclitaxel, and doxorubicin. studies revealed five potent compounds with good physicochemical and ADMET profiles and potent interactions with key anticancer targets (EGFR, DHFR, VEGFR2, CDK2, mTOR, and PI3K) compared to reference drugs. This work paved the way for the synthesis of more potent compounds based on the phenylamino--triazine scaffold and the exploration of their diverse and potential biological activities as well as their mechanisms of action.
通过两种不同方法（回流法和微波辅助法）设计并合成了一系列对称三取代三嗪衍生物。通过红外光谱（IR）、核磁共振（¹H NMR和¹³C NMR）以及质谱确定了化合物的结构。微波辅助法的产率（91 - 98%）显著高于回流法（80 - 88%），高出约10%，同时反应时间显著更短（15 - 30分钟）。化合物3b对MCF7（人乳腺癌）细胞系显示出良好的细胞毒性活性，IC值为6.19 μM。化合物3a和2e对C26（结肠癌）细胞系显示出较强的细胞毒性活性，IC值分别为1.21和8.28 μM。化合物3e对MCF7和C26细胞系均显示出良好的细胞毒性活性，IC值分别为13.74和14.66 μM。特别地，化合物2d在合成化合物中对MCF7和C26细胞系均表现出最强的细胞毒性活性，IC值分别为6.54和0.38 μM。此外，与化合物2d、3a、紫杉醇和阿霉素相比，化合物2e、3a和3e对癌细胞系具有更高的选择性，对BAEC（牛主动脉内皮）正常细胞的毒性更低。研究表明，与参考药物相比，有五种活性化合物具有良好的物理化学性质和ADMET特性，并且与关键抗癌靶点（EGFR、DHFR、VEGFR2、CDK2、mTOR和PI3K）有强效相互作用。这项工作为基于苯氨基三嗪支架合成更有效的化合物以及探索它们多样的潜在生物活性及其作用机制铺平了道路。
