Synthesis and cytotoxicity evaluation of ibuprofen amide derivatives on MCF-7 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 synthesize and evaluate the cytotoxic activity of ibuprofen amide derivatives against MCF-7 breast cancer cells. These compounds were synthesized using a one-pot method from ibuprofen and aromatic amines, achieving yields ranging 12.1-40.2%. The ability to inhibit the growth of cancer cells was then assessed by the MTT assay. Drug-like properties were analyzed based on Lipinski’s Rule of Five to predict oral availability, and pharmacokinetic and toxicological parameters were predicted with ADMETlab 3.0. All five ibuprofen amides had cytotoxic activity against MCF-7 cells, with IC₅₀ values ranging from 13.93 to 44.17 µM. Compound T5 (N-(3-bromopyridin-4-yl)-2-(4-isobutylphenyl) propanamide) displayed the highest potency. These compounds demonstrated favorable pharmacokinetic properties and no significant predicted toxicity, suggesting their potential for development as breast cancer therapeutics.