title: 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.
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale A. Doria 6, I-95125 Catania, Italy. ctringali@unict.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Spatafora
authors.forename: Vincenza
authors.initials: V
authors.lastname: Barresi
authors.forename: Vedamurthy M
authors.initials: VM
authors.lastname: Bhusainahalli
authors.forename: Simone
authors.initials: S
authors.lastname: Di Micco
authors.forename: Nicolò
authors.initials: N
authors.lastname: Musso
authors.forename: Raffaele
authors.initials: R
authors.lastname: Riccio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Daniele
authors.initials: D
authors.lastname: Condorelli
authors.forename: Corrado
authors.initials: C
authors.lastname: Tringali
mesh_terms: D000577:Amides / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000737:chemistry; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014966:Xanthenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D002109:Caffeic Acids; D004952:Esters; D017705:Lignans; D014966:Xanthenes; C577829:bis(2-phenylethyl)-6,9,10-trihydroxybenzo(kl)xanthene-1,2-dicarboxylate; D004247:DNA