Synthesis and Characterization of Biologically Active 1,2,4‐Triazole‐Naphthyridine Scaffolds as Potential Anticancer Agents

ABSTRACT The synthesis of new molecules with potent anticancer activity remains a key objective in medicinal chemistry. A new series of biologically active 2,4‐dimethyl‐9‐aryl‐[1,2,4]triazolo[4,3‐ a ][1,8]naphthyridine scaffolds ( 6a–h ) was synthesized and confirmed by the 1 H NMR, 13 C NMR, and mass spectrometry data. The synthesized derivatives were evaluated for the biological evaluation of anticancer activity against four human cancer cell lines, MCF‐7 (breast cancer), Colo‐205 (colon cancer), SiHa (cervical cancer), and A549 (lung carcinoma) by using the MTT assay method. All the tested compounds showed significant anticancer activity. Predominantly, two compounds, 6g and 6b , demonstrated the highest anticancer activity with IC 50 values of ( 6b ) 6.64 ± 0.44 μM (MCF‐7), 9.03 ± 0.36 μM (Colo‐205), 10.28 ± 0.25 μM (SiHa), 12.23 ± 1.54 μM (A549), 8.16 ± 0.31 μM (MCF‐7), 13.27 ± 0.54 μM (Colo‐205), 12.05 ± 0.22 μM (SiHa), 16.07 ± 0.15 μM (A549). Structure–activity relationship (SAR) studies revealed that the presence of electron‐donating groups significantly enhanced anticancer activity, whereas electron‐withdrawing substituents led to a reduction in potency. Halogen substitutions exhibited moderate anticancer activity.