Allyl-functionalized calix[4]resorcinarenes against breast cancer cells: Synthesis, cytotoxicity, apoptosis induction, and computational insights

The present study is intended as an initial exploration of allyl-functionalized calix[4]resorcinarenes (4a-4f) as cytotoxic agents. These derivatives were obtained via the O-allylation of 3-methoxy-4-hydroxybenzaldehyde (vanillin) and 4-hydroxybenzaldehyde with resorcinol, pyrogallol, or 2-methylresorcinol. All compounds were examined for their in vitro Anticancer activity against human breast Cancer cell lines (MDA-MB-231 and MCF-7). Among them, analogue 4a exhibited moderate cytotoxicity in breast Cancer cell lines, i.e., MCF-7 cells (IC₅₀ = 8.27 μM), showing notable cytotoxicity in the low micromolar range, comparable to that of cisplatin and within the same order of magnitude as doxorubicin. Accompanied by Apoptosis profiling, compound 4a at 1 × and 2 × IC₅₀ showed a concentration-dependent increase in Apoptosis cell death compared to untreated controls. Meanwhile, computational studies were conducted to explore potential interactions with EGFR as a putative target, suggesting that compound 4a may possibly interact with EGFR through hydrogen bonding and hydrophobic contacts.

Allyl; Apoptosis; Breast cancer; Calix[4]resorcinarenes; Molecular docking.