Synthesis and cytotoxic evaluation of ibuprofen amide derivatives on MCF-7 breast cancer cells

Abstract

Ibuprofen, a non-steroidal anti-inflammatory drug, has been documented in clinical studies for its potential to reduce breast cancer risk. The research direction exploring novel ibuprofen derivatives with anticancer activity has attracted significant attention from scientists, particularly amide derivatives. This study was conducted to synthesise and evaluate the cytotoxic activity of ibuprofen amide derivatives against MCF-7 breast cancer cells. These compounds were synthesised using a one-pot method from ibuprofen and aromatic amines, achieving yields ranging from 12.1 to 40.2%. The ability to inhibit the growth of cancer cells was then assessed by the MTT assay. Drug-like properties were analysed based on Lipinski’s Rule of Five to predict oral availability, while pharmacokinetic and toxicological parameters were predicted using ADMETlab 3.0. The results reveal that all five ibuprofen amides had cytotoxic activity against MCF-7 cells, with IC₅₀ values ranging from 13.93 to 44.17 µM, in which compound T5 (N-(3-bromopyridin-4-yl)-2-(4- isobutylphenyl) propanamide) displayed the highest potency. These compounds demonstrated favourable pharmacokinetic properties, providing an initial foundation for further evaluation of the selectivity, mechanism of action, and safety of the derivatives.