eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-05-20 19 2 71841 article Kalpana Divekar 1 Chanda Ranjan 2 Department of Pharmaceutical Chemistry, College of Pharmaceutical Sciences, Dayananda Sagar University, Kumarswamy Layout, Bangalore, India. Department of Pharmaceutical Chemistry, The Oxford College of Pharmacy, Bengaluru, Karnataka, India A set of novel heterocyclic oxadiazoles 3-(4-acetyl-5-substituted-phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-substituted-2H-coumarin derivatives (D1-D8) was designed and synthesised with the potential to act as EGFR inhibitors to treat cancer. The synthesised compounds (D1-D8) were tested for EGFR inhibition potential in this investigation.Among the compounds tested, D4 and D8 showed promising cytotoxic activity. Specifically, compound D8 showed IC₅₀ values of 10.85 ± 0.027 μM for A549 (lung cancer), 7.42 ± 0.034 μM for MCF7 (breast cancer), 8.92 ± 0.041 μM for MDA:MB:231 (triple-negative breast cancer), and compound D4 exhibited IC₅₀ values of 7.96 ± 0.021 μM for A549, 5.67 ± 0.035 μM for MCF-7, and 9.08 ± 0.034 μM for MDA-MB-231. Notably, the EGFR inhibitory activity of compound D4 (IC₅₀, 0.4801 µM) exhibited similar potency to the standarderlotinib (IC₅₀, 0.4078 µM), and  D8 (IC₅₀, 0.5157 µM) demonstrated less activity compared to erlotinib against MCF-7 breast cancer cells. The docking results for ligands D4 and D8 have also favourable binding activity, closely matching the potency of the standard drugerlotinib. https://biomedpharmajournal.org/vol19no2/design-and-synthesis-of-134-oxadiazole-coumarin-hybrids-as-egfr-inhibitors-molecular-docking-studies-and-in-vitro-anticancer-evaluation/ Coumarins EGFR inhibitors Molecular hybridization 1 3 4-oxadiazoles Pharmacophore modelling