Unit:
Τομέας ΦΑΡΜΑΚΟΓΝΩΣΙΑΣ ΚΑΙ ΧΗΜΕΙΑΣ ΦΥΣΙΚΩΝ ΠΡΟΪΟΝΤΩΝLibrary of the School of Science
Dissertation committee:
Αλέξιος-Λέανδρος Σκαλτσούνης Καθηγητής, Σοφία Μιτάκου Καθηγήτρια, Νεκτάριος Αληγιάννης Αναπλ. Καθηγητής (Επιβλέπων)
Original Title:
Discovery of tyrosinase inhibitors and antioxidants involving a high-throughput bioguided approach, employing modern analytical methodologies and multivariate statistics
Translated title:
Ανάπτυξη βιοκατευθυνόμενης μεθοδολογίας υψηλής απόδοσης για την ανακάλυψη αναστολέων τυροσινάσης και αντιοξειδωτικών φυσικών προϊόντων, χρησιμοποιώντας σύγχρονες αναλυτικές τεχνικές και πολυπαραγοντική στατιστική
Summary:
The scope of the present dissemination was the discovery of plant derived
antioxidants and tyrosinase inhibitors from high biodiversity regions utilizing
miniaturized high-throughput screening (HTS) technologies and the introduction
of an integrated methodology for the rapid identification of bioactive
compounds during bioassay-guided procedures.
An extended extract library (3600 extracts, 150 plant families) was generated
from plants originated from six hotspot regions and screened for three
biological targets; antioxidant, UV-protection and tyrosinase inhibition. A
unique chemical library (480 pure compounds) aimed to determine the promising
chemical structures for the demonstration of the aforementioned activities. A
statistical treatment of the screening results allowed the disclosure of
parameters (country of origin, plant family, extraction solvent and plant part)
that contribute best to the appearance of high anti-tyrosinase and antioxidant
activity.
The combination of a stepwise-elution CPC for the fractionation and a activity
profiling in TLC, provided useful indications of potential bioactive compounds
in the active extracts, rendering the bioguided isolation process more targeted
to specific candidates.
In the last chapter, multivariate data analysis tools supported the development
of an integrated HPTLC-based procedure, for the tracing and targeted isolation
of the compounds that exhibit the highest bioactivity in fractions of Morus
alba extract, the most prominent anti-melanogenic agent identified during
screens. Two methodologies were developed for the generation of the dataset;
one based on chromatogram binning and one on manual peak picking. All steps of
the experimental procedure implemented techniques that afford essential key
elements, for application in HTS procedures for drug discovery purposes.
Keywords:
Tyrosinase inhibition, Antioxidant, Biodiversity, HPTLC, Morus alba
Number of references:
182
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