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Tesi etd-02272013-175756


Thesis type
Tesi di dottorato di ricerca
Author
FAIELLA, LAURA
URN
etd-02272013-175756
Title
Isolation and structural characterization of diterpenoidic compounds and identification of their molecular targets
Settore scientifico disciplinare
BIO/15
Corso di studi
FISIOPATOLOGIA CLINICA E SCIENZE DEL FARMACO
Commissione
tutor Prof. Braca, Alessandra
Parole chiave
  • Podocarpus
  • phytochemical studies
  • diterpenes
  • Cle
Data inizio appello
27/03/2013;
Consultabilità
completa
Riassunto analitico
As part of an ongoing research program on plants biosynthesizing diterpenes, it was performed a project aimed to create a diterpenes library from different plant’s species. The attention was paid on plants known to be rich on diterpenes, since they are a class of natural terpenoids with a great structural variability and a wide spectrum of biological activities. <br>Podocarpus elongatus (Aiton) L’Hèr. ex Pers, Podocarpus gracilior Pilger (Podocarpaceae), Clerodendrum splendens G. Don. (Verbenaceae), and Sideritis pullulans Vent. (Lamiaceae) were selected.<br>The new diterpenes nagilactone C 7-O-alpha-L-arabinopyranosyl-(1-4)-beta-D-xylopyranoside, nagilactone C 7-O-beta-D-glucopyranosyl-(1-4)-beta-D-xylopyranoside, nagilactone C 7-O-beta-D-xylopyranoside, nagilactone A 7-O-alpha-L-arabinopyranosyl-(1-4)-beta-D-xylopyranoside, 2beta,15S,16,17,19-pentahydroxy-isopimar-8(14)-ene 17-O-beta-D-glucopyranoside, 2beta,15R,16,17,19-pentahydroxy-isopimar-8(14)-ene 17-O-beta-D-glucopyranoside, and the known diterpenes 4-carboxy-19-nor-totarol, nagilactone B, and nagilactone C were isolated from P. elongatus leaves.<br>The new diterpenes 2alpha,16-dihydroxy-4beta-carboxy-O-beta-D-glucopyranosyl-19-nor-totarol, nagilactone K together with the known nagilactone B, nagilactone C, nagilactone D, and podolactone B were isolated from P. gracilior leaves.<br>The new diterpenoidic compounds 2alpha-acetoxy-3beta-(2’,3’-diacetoxy-2’-methyl)-butanoyloxy-14-hydro-15-hydroxyclerodin, 3,15-dihydroxy-14-hydro-clerodin, 2alpha,15-dihydroxy-3beta-(2’-hydroxy-3’-acetoxy-2’-methyl)-butanoyloxy-6alpha,18-diacetoxy-4alpha,17-epoxy-clerodan-11,16-lactone, 3beta,14S,15-trihydroxy-6alpha,18-diacetoxy-4alpha,17-epoxy-clerodan-11,16-lactone, and the only known 14,15-dihydroxy-3-epicarioptin were found in C. splendens leaves. <br>The new diterpenes, ent-1α,3α,7β,18-tetrahydroxykaur-16-ene, ent-3α,11α,18-trihydroxy-17-norkauran-16-ene, ent-3α,7β,18-trihydroxy-17-norkauran-16-one, ent-3α,7β-dihydroxy-18-acetyloxy-17-norkauran-16-one, ent-3α,7β,16α,17-tetrahydroxy-18-acetyloxy-kaurane, ent-7β,16α,17,18-tetrahydroxykaurane, and the known foliol, linearol, ent-3α,7β,17-trihydroxy-18-acetyloxy-15α,16α-epoxykaurane were isolated from S. pullulans leaves. <br>Finally, some diterpenes of our library were subjected to a chemical proteomics study as a strategy for the molecular target identification of natural bioactive compounds, setting up a method for the research of their molecular targets.<br>A fishing for partners study reveals Hsp70 and PPARγ as potential proteic target of 15-ketoatractyligenin methyl ester, a semi-synthetic ent-kaurane, while studies based on limited proteolysis-mass spectrometry strategy, free cell assays, and pro-apoptotic activity of hardwiickik acid in human monocytes allowed to validate Hsp27 as target for the clerodane diterpene.<br><br>
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