Synthesis, antioxidant, and antiproliferative activity of apocynin triazole derivatives containing 3,4-difluorophenyl-cyclopropanamine motif

Apocynin is a natural product known for its antioxidant activity and potential medicinal applications. However, it is still unexplored in semisynthetic strategies. Considering the need for the development of new therapeutic alternatives for cancer treatment, this work explored the reactivity of apocynin towards the synthesis of potential triazole-based antineoplastic compounds inspired by histone lysine demethylase-specific 1 (LSD1) inhibitors and minor groove binders and evaluated their cytotoxic activity in the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7) and antioxidant activity, comparing them to bromine analogues. As a result, apocynin derivative 7b showed promising growth inhibition (GI50 = 15.5 µM) and low antioxidant activity. The cell cycle analysis showed increased cell arrest in the G1 phase, corroborating potential inhibition of LSD1. This work provided new insights into the synthetic use of apocynin and identified an interesting compound for further studies.