Synthesis, Biological Assessment, and Molecular Docking of New Indoline‐Pyrazine Hybrids as Promising Anticancer Agents

ABSTRACT In the present work, we synthesized a novel library of indoline‐pyrazine hybrids involving Buchwald coupling, Suzuki–Miyaura coupling, and Ulmann reactions. The new analogues were screened for their in vitro anticancer activity against MCF‐7 and MDA‐MB‐231 cell lines, using doxorubicin as a reference, by the MTT test. Compound 7d displayed potent activity against both cell lines with IC 50 values of 8.72 ± 0.88 µM and 9.54 ± 0.85 µM , respectively. Compound 7c was observed to be the second most active compound with an IC 50 value of 10.45 ± 1.02 µM and 9.59 ± 1.08 µM . Compound 7a showed promising activity with an IC 50 value of 11.19 ± 1.03 µM and 12.34 ± 1.07 µM . Compound 7 g presented a good activity with an IC 50 value of 14.54 ± 1.03 µM and 15.35 ± 1.05 µM . Molecular docking studies performed against the crystal structure of epidermal growth factor receptor (EGFR) with potent ligands 7c and 7d demonstrated a promising docking score and meaningful binding interactions, especially H‐bonds. Predicted ADME properties presented their favorable drug‐like properties.