Synthesis and biological evaluation of novel nitrogen-containing heterocyclic derivatives as potential anticancer agents.

Based on screening results, a series of nitrogen-containing five-membered heterocyclic compounds were designed and synthesized for anticancer evaluation. Among them, 7s, featuring a 1,2,3-triazole scaffold, exhibited the most potent antiproliferative activity against four human cancer cell lines (IC₅₀ < 10 μM). Mechanistic studies revealed that 7s downregulated phosphorylated AKT (p-AKT) protein at 5 μM. It also demonstrated moderate metabolic stability (T₁/₂ = 38.9 min, clearance = 23.4 mL/min/kg) and acceptable aqueous solubility (2.6 mg/100 mL). SwissADME predictions confirmed its good oral bioavailability and gastrointestinal absorption. Importantly, 7s showed low cytotoxicity toward normal HEK293 cells (IC₅₀ = 56.2 μM), suggesting a favorable safety. These results support 7s as a promising lead compound for further development in anticancer drug discovery.