Microwave‐Assisted Synthesis and Biological Evaluation of Phenolic‐ <i>s</i> ‐Triazine Hybrids

ABSTRACT A new series of phenolic compounds was synthesized from benzoic and cinnamic acyl chlorides. The resulting phenols were reacted with 2‐aminoethanol, and the subsequent alcohols 2a‐d and 5a‐e were treated with cyanuric chloride under microwave irradiation to yield the target molecules 3a‐d and 6a‐e , respectively. The reactions proceeded in good yields (up to 75%). Compound 10 was prepared analogously using mono‐ N ‐Boc‐protected ethylenediamine. All new compounds were characterized by FT‐IR, NMR, and HRMS. Prediction analysis identified apurinic/apyrimidinic endonuclease 1 (APE1) and glycine transporter 2 (GlyT2) as potential molecular targets. Molecular docking revealed that compound 3b had the strongest binding affinity to APE1 (−9.0 kcal/mol), forming a key interaction with the active‐site Mg 2 + ion. Compound 10 showed the highest affinity for GlyT2 (−10.9 kcal/mol). Several compounds demonstrated significant cytotoxicity against A549 and H1299 cell lines. Compounds 3a , 6d , and 10 were potent against both. Compound 3b was particularly effective against H1299 cells (IC 50 = 17.31 µg/mL), while 6a and 6c showed selectivity for A549 cells. These results indicate the synthesized compounds are promising candidates for further development.