Abstract
A library of novel ibuprofen-appended benzoxazole analogues (7a-l) was synthesized via a series of nitration, reduction, and condensation-cyclization reactions and screened for their in vitro anticancer activity against human breast cancer MCF-7 and MDA-MB-231 cell lines using doxorubicin as a standard reference. Compounds 7h and 7j displayed outstanding activity against the MCF-7 cell line with an IC(50) value of 8.92 ± 0.91 μM and 9.14 ± 8.22 μM, respectively, compared to the doxorubicin IC(50) value of 9.29 ± 1.02 μM. Compound 7h also exhibited outstanding activity against the MDA-MB-231 cell line with an IC(50) value of 7.54 ± 0.95 μM compared to the doxorubicin IC(50) value of 7.68 ± 5.36 μM. Compounds 7h, 7i, 7j, and 7g showed identical morphological changes to those showed by doxorubicin. The molecular docking study against ERα unveiled their best docking scores and binding interactions in agreement to experimental results. Pharmacokinetics prediction envisaged their drug-like properties suitable for therapeutic applications.