title: Flavanocoumarins from Guazuma ulmifolia bark and evaluation of their affinity for STAT1.
abstract: From the bark of Guazuma ulmifolia, a plant used as anti-inflammatory remedy, the flavanocoumarin epiphyllocoumarin (1) along with epiphyllocoumarin-[4β→8]-(-)-epicatechin (2) and epiphyllocoumarin-[4β→8]-(-)-epicatechin-[4β→8]-(-)-epicatechin (3), never reported before, have been isolated. The structures of the proantocyanidins 2-3 have been elucidated by extensive NMR and ESI-MS analysis. On the basis of the flavane nature of the isolated compounds and considering the strong anti-STAT1 activity reported for epigallocatechin 3-O-gallate (EGCG), the affinity of compounds 1-3 for STAT1 has been evaluated by Surface Plasmon Resonance. Compounds 1-2 showed affinity for STAT1 comparable to that exerted by EGCG. In order to confirm this result, molecular docking studies to evaluate the interactions of compounds 1-3, phyllocoumarin (4), the reference compound EGCG (5), and its related compound (+)-gallocatechin 3-O-gallate (6) with STAT1 have been carried out. Furthermore the ability of compounds 1-3 to inhibit STAT1 activation has been evaluated using a nuclear extract obtained from the human monocytic leukemia cell line TPH-1. Flavanocoumarins 1-2 inhibited STAT1-DNA binding.
authors.affiliation: Dipartimento di Scienze Farmaceutiche e Biomediche, Università degli Studi di Salerno, Fisciano (SA), Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Maldini
authors.forename: Simone
authors.initials: S
authors.lastname: Di Micco
authors.forename: Paola
authors.initials: P
authors.lastname: Montoro
authors.forename: Elena
authors.initials: E
authors.lastname: Darra
authors.forename: Sofia
authors.initials: S
authors.lastname: Mariotto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Cosimo
authors.initials: C
authors.lastname: Pizza
authors.forename: Sonia
authors.initials: S
authors.lastname: Piacente
mesh_terms: D002460:Cell Line; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D006801:Humans; D019660:Malvaceae / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D003374:Coumarins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D004247:DNA