Marine environment is prolific in organisms with unique properties. Seas and oceans contain a wide diversity of species with biologically active metabolites that represent a valuable source with great potential for the development of novel therapeutic agents. This dissertation is focused on the biological study of synthetic compounds based on marine scaffolds as well as on marine natural product extracts originating from the Aegean Sea. Furthermore, it offers an introduction on the importance of marine natural products in the search of new bioactive compounds, the use of natural products as scaffolds for the synthesis of new drugs, and a general overview on bioactivity screening and the current status of marine-derived bioactive compounds as therapeutic agents.
The potential of oroidin and clathrodin as parent structures for synthesis of novel compounds was explored. Antimicrobial and antiproliferative studies were conducted and it was concluded that 4-phenyl-2-aminoimidazoles 6g(I) and 6h(I) showed the best antimicrobial effect against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus), while compound 6j(I) showed the most interesting IC50 in antiproliferative studies. Compound 7(II), a synthetic derivative of 2-aminobenzothiazole, showed IC50 of 16 μM and 71 μM against a cancer cell line and a normal cell line, respectively. The selectivity index showed selectivity towards cancerous cells. In addition, okadaic acid was used as inspiration for the synthesis of crown ether acyl compounds. Compound (1,4,7,10,13,16-hexaoxacyclooctadecan-2-yl)methyl 3-(pyren-1-yl)propanoate) 1o(III) was found to be the most active in antimicrobial studies against Gram-positive Staphylococcus aureus with a MIC50 of 7.2 μM.
The importance of bioprospecting the rich marine biodiversity in the Aegean Sea was also studied in this thesis. Biological activities of extracts from cyanobacteria, micro- and macroalgae were evaluated, and microalgae extracts (Amphora cf capitellata and Nitzschia communis) showed the most interesting antimicrobial results against Staphylococcus aureus and fungus Candida albicans.
The results of the biological studies conducted in this thesis demonstrated antimicrobial and antiproliferative activity of several marine natural products and their synthetic derivatives. Further studies and structural optimization should be done to fully explore their potential for the development of therapeutic agents.