Background: Coumarin is a natural phytochemical but as such has no medical uses. However, various
natural and synthetic coumarin analogs attract attention due to their interesting biological properties.
Objective: Here, we evaluated and compared anticancer properties of a new synthetic hybrid compound AD-
013, which integrates a coumarin moiety and an α-methylene-δ-lactone motif, with novobiocin, a natural antibiotic
bearing a coumarin scaffold.
Methods: Cytotoxic activities of compound AD-013 and novobiocin were assessed by the MTT assay. In order
to explore the mechanism of anticancer activity of analog AD-013, we performed quantitative real-time PCR
analysis of apoptosis- and cell cycle-related genes. The ability of AD-013 and novobiocin to induce apoptosis
and DNA damage was studied by flow cytometry.
Results: The cytotoxic activity of this new compound was compared with the activity of a coumarin-based antibiotic
novobiocin against two cancer cell lines, MCF-7 and HL-60 and also against normal human cells, MCF-
10A and HUVEC. AD-013 was much more cytotoxic than novobiocin in both cancer cell lines and showed
some selectivity against MCF-7 cancer cells as compared with MCF-10A healthy cells. Expression levels of the
pro-apoptotic genes significantly increased while the anti-apoptotic genes, were down-regulated for both compounds
in both cancer cell lines.
AD-013 was able to inhibit cell proliferation, generate DNA damage and induce apoptosis. The obtained data
showed that this compound caused the cell cycle arrest in subG0/G1 in both cancer cell lines.
Conclusion: The new hybrid analog was a much stronger apoptosis inducer than novobiocin and activated the
intrinsic pathway of apoptosis.