In vitro anticancer studies of new derivatives based on the furanocoumarin scaffold

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.

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Journal
Scientific Reports
Published
2025-12-04
DOI
https://doi.org/10.1038/s41598-025-30998-z
Primary Topic
Synthesis and biological activity
Type
article
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article

In vitro anticancer studies of new derivatives based on the furanocoumarin scaffold

Ewa Augustynowicz–Kopeć, Wioletta Olejarz, Mariola Napiórkowska, Daniel Szulczyk et al.
Scientific Reports
Synthesis and biological activity
article

In vitro anticancer studies of new derivatives based on the furanocoumarin scaffold

Ewa Augustynowicz–Kopeć, Wioletta Olejarz, Mariola Napiórkowska, Daniel Szulczyk, Agnieszka Filipek, Agnieszka Głogowska, Tomasz Szostek
article en

Abstract

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.

Scientific ReportsVol. 16(1)
Medical University of Warsaw (PL)
Openalex Percentile: Top 71%
Synthesis and biological activity
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