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Preclinical Assessment of the Bioactivity of the Anticancer Coumarin OT48 by Spheroids, Colony Formation Assays, and Zebrafish Xenografts
Published on: June 26, 2018
In vitro anticancer studies of new derivatives based on the furanocoumarin scaffold
Wioletta Olejarz1,2, Ewa Augustynowicz-Kopeć3, Agnieszka Głogowska3
1Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097, Warsaw, Poland.
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.
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