Unit:
Τομέας ΦΑΡΜΑΚΟΓΝΩΣΙΑΣ ΚΑΙ ΧΗΜΕΙΑΣ ΦΥΣΙΚΩΝ ΠΡΟΪΟΝΤΩΝLibrary of the School of Science
Dissertation committee:
Αλέξιος-Λέανδρος Σκαλτσούνης Καθηγητής
Original Title:
Alternative Natural Sources of Indirubin Derivatives. Analysis thereof in Plasma and Tissues – Toxicological studies.
Translated title:
Εναλλακτικές Φυσικές Πηγές Παραγώγων Ινδιρουβίνης. Ανάλυση Αυτών Στο Πλάσμα Και Στους Ιστούς - Τοξικολογικές Μελέτες.
Summary:
Indirubins are bis-indole alkaloid compounds occurring naturally in various
indigo-containing plants and mollusk gastropods. These molecules were initially
known for their long history in the dye industry. However, during the last two
decades, the chemical and biological studies of indirubins have increased
tremendously due to the discovery of their bio-activities against numerous
human cancer cell lines mainly through the inhibition of protein kinases.
Therefore, the aim of this work was firstly to several potential new sources of
indirubins using a UHPLC-ESI-MS/MS platform.Thus, three marine mollusks
(Hexaplex trunculus, Rapana venosa, and Plicopurpura pansa), one plant (Isatis
tomentella), and one pharmaceutical product (Danggui Longgui Wan) were analyzed
for the identification of the indirubins thereof. The indirubins and the major
components of the mollusk Hexaplex trunculus and the plant Isatis tomentella
were further isolated using newly developed FCPC methodology.The glands of R.
venosa were studied here for the very first time; several extracts were
produced and analyzed.The ethyl acetate extract which was the richest in
secondary metabolites revealed in LC-MS-ESI(-) the presence of several
brominated and non-brominated indirubin precursors namely. The milk of P.
pansadisplayed eleven brominated compounds, among which eight are previously
reportedand three are unknown.Indirubin and indigo were detected in I.
tomentella which also contained several amino acids, nucleosides, glycosylated
and non-glycosylated flavonoids. A total of forty-six metabolites were detected
in this extract and its major constituents were isolated using step-gradient
CPC technique, and structurally elucidated using NMR and HRMS technique and
comparison to data in the literature.
Keywords:
Indirubins, Metabolomics, Pharmacokinetics, Toxicology, LC-HRMS
Number of references:
172
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