Dissertation committee:
Μαρία Ζερβού, Ερευνήτρια Β΄, Εθνικό Ίδρυμα Ερευνών
Ευσταθία Ιωάννου, Επίκουρη Καθηγήτρια, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Θωμάς Μαυρομούστακος, Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Σοφία Μητάκου, Καθηγήτρια, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Βασίλειος Ρούσσης, Καθηγητής, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Ελένη Σκαλτσά, Καθηγήτρια, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Όλγα Τζάκου, Καθηγήτρια, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Summary:
Due to the uniqueness of the marine environment, natural products isolated from marine organisms often present differentiated chemical structures exhibiting a wide range of biological activities through specialized mechanisms. Several pharmaceutical drugs with the active substance being of marine origin are already on the market, while a significant number is currently in preclinical and clinical trials. In addition, marine natural products find applications in the fields of cosmetology, nutrition, biotechnology and materials science. In recent years, marine microorganisms have attracted constantly increasing attention as they have been proven to be a rich source of novel bioactive molecules with novel carbon skeletons or uncommon functional groups.
In the framework of the present PhD thesis, the chemical composition of the organic extracts obtained after large scale cultivation of four selected bacterial strains isolated from marine sediments collected in the Aegean (Milos) and Ionian (Kefalonia and Kerkyra) Seas was investigated. The extracts were subjected to a series of chromatographic separations to result in the isolation of their secondary metabolites, the chemical structures of which were elucidated on the basis of the analysis of their spectroscopic data (mainly NMR and MS). In total, 78 different secondary metabolites were isolated, 75 of which have so far been identified. Among these, 12 are new natural products, while 6 were isolated for the first time from a natural source.
Twenty-five secondary metabolites were isolated and identified from Bacillus endophyticus BI0327 strain, including: (i) nine 2,5-diketopiperazines (2,5-DKPs), (ii) three indole derivatives, (iii) one naphthoquinone, (iv) two triterpenes, (v) eight simple aromatic derivatives and (vi) two methacrylic acid derivatives, two of which are new natural products, whereas one was isolated for the first time from a natural source.
Two secondary metabolites were isolated and identified from Streptomyces althioticus BI0850 strain, including one 2,5-DKP and one simple nitrogenous compound.
Forty-four secondary metabolites were isolated and identified from Streptomyces smyrnaeus BI0918 strain, including: (i) twenty-four 2,5-DKPs, one of which is a new natural product, (ii) seven benzodiazepine derivatives, four of which are new natural products, whereas two were isolated from the first time from a natural source, (iii) an indole derivative, (iv) two nucleoside derivatives, (v) two other nitrogen compounds, one of which was isolated for the first time from a natural source, (vi) a simple sulfur-containing compound, (vii) two derivatives of benzoic acid, (viii) one simple glycerol derivative, (ix) a methacrylic acid derivative which is a new natural product and (x) three high molecular weight polyether metabolites.
Thirty-four secondary metabolites were isolated and identified from Bacillus subtilis strain BI0980, including: (i) nineteen 2,5-DKPs, two of which are new natural products and one was isolated for the first time from a natural source, (ii) three indole derivatives, (iii) one nucleoside derivative, (iv) one flavonoid, (v) five benzoic acid derivatives, (vi) four metabolites of different chemical classes, two of which are new natural products and one was isolated for the first time from a natural source and (vii) a methacrylic acid derivative.
The evaluation of the biological activity of the metabolites isolated in sufficient quantities is currently in progress.
Keywords:
bioactive natural products, secondary metabolites, isolation, structure elucidation, marine-derived microorganisms, marine sediments, Aegean and Ionian Seas
