Novel Sulfonamide–Triazine Hybrid Derivatives: Docking, Synthesis, and Biological Evaluation as Anticancer Agents

[Image: see text] The biological benefits of trisubstituted 1,3,5-triazine derivatives include their ability to reduce inflammation and fight cancer. A unique series of sulfonamide–triazine hybrid molecules were produced chemically by synthesizing triazine derivatives utilizing the usual nucleophilic aromatic substitution of cyanuric chloride via the solvent-free/neat fusion method. Fourier-transform infrared spectroscopy (FTIR), (1)H NMR, and (13)C NMR spectroscopic analyses were used to identify novel trisubstituted synthetic compounds. The synthesized compounds have a moderate inhibition percentage when tested at 100 μM against the phosphoinositol 3-kinases (PI3Kα) enzyme; compounds 20 and 34 showed 46 and 68% anti-PI3Kα activity, respectively. To comprehend the anticipated interactions, the most successful compounds were subsequently docked into a PI3Kα protein’s binding site (PDB code: 6OAC, resolution: 3.15 Å). The final synthetic compounds’ anticancer activity was tested on the breast (MCF-7) and lung (A549) cancer cell lines at doses of 100 and 50 μM for additional evaluation of anticancer characteristics. The IC(50) values for the sulfaguanidine–triazine derivatives 27, 28, 29, 31, and 35 ranged from 14.8 to 33.2 μM, showing that compounds containing sulfaguanidine and diethylamine in their structures significantly inhibited the activity. Compound 34 could be a promising lead compound for developing new target-selected anticancer compounds with low toxicity and high selectivity.