Furanocoumarins, known for their diverse bioactivity, were chemically modified to develop new derivatives with potential anticancer properties. This study reports the synthesis and comprehensive biological evaluation of seven aminoalkyl furanocoumarin derivatives. In vitro cytotoxicity was assessed against four human cancer cell lines (HTB-140, A549, HeLa, SW620) and a normal keratinocyte line (HaCaT) using MTT and LDH assays. Compounds 4 and 6 demonstrated the strongest antiproliferative effects, particularly against SW620 and HTB-140 cells, with IC₅₀ values around 11-18 µM, indicating potent anticancer activity. Flow cytometry revealed that these effects were largely mediated through apoptosis, not nonspecific toxicity. Molecular docking studies identified interactions with EGFR and Bcl-2 family proteins, suggesting a pro-apoptotic mechanism, though additional pathways may contribute to their selectivity. Importantly, antimicrobial screening showed negligible activity against representative Gram-positive and Gram-negative strains, indicating a low risk of microbiota disruption - an important feature for cancer therapy. These findings position furanocoumarin derivatives, particularly compounds 4 and 6, as promising lead structures for the development of selective, microbiota-sparing anticancer agents.
Olejarz et al. (Thu,) studied this question.