Symmetrical di-substituted phenylamino--triazine derivatives as anticancer agents: and approach.

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.