Issue 17, 2014

Bio-inspired benzo[k,l]xanthene lignans: synthesis, DNA-interaction and antiproliferative properties

Abstract

In this work twelve benzo[k,l]xanthene lignans were synthesized by biomimetic, Mn-mediated oxidative coupling of caffeic esters and amides. These compounds, bearing different flexible pendants at position C1/C2 of the aromatic core, interact with DNA in a dual mode, as confirmed by DF-STD NMR analysis and molecular docking: the planar core acts as a base pair intercalant, whereas the flexible pendants act as minor groove binders. Their antiproliferative activity was evaluated on a panel of six tumor cell lines: HT-29, Caco-2, HCT-116 (human colon carcinoma), H226, A549 (human lung carcinoma), and SH-SY5Y (human neuroblastoma). All compounds under study, except 29, resulted in activity against one or more cell lines, and the markedly lipophilic esters 13 and 28 showed the highest activity. Compound 13 was more active than the anticancer drug 5-fluorouracil (5-FU) towards HCT-116 (colon, GI50 = 3.16 μM) and H226 (lung, GI50 = 4.33 μM) cell lines.

Graphical abstract: Bio-inspired benzo[k,l]xanthene lignans: synthesis, DNA-interaction and antiproliferative properties

Supplementary files

Article information

Article type
Paper
Submitted
17 Dec 2013
Accepted
21 Feb 2014
First published
21 Feb 2014

Org. Biomol. Chem., 2014,12, 2686-2701

Bio-inspired benzo[k,l]xanthene lignans: synthesis, DNA-interaction and antiproliferative properties

C. Spatafora, V. Barresi, V. M. Bhusainahalli, S. Di Micco, N. Musso, R. Riccio, G. Bifulco, D. Condorelli and C. Tringali, Org. Biomol. Chem., 2014, 12, 2686 DOI: 10.1039/C3OB42521E

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