engleski

Antiproliferative properties of synthetic granulatamide B and its structural analogues

Gorgonian corals of the genus Eunicella have been shown as a rich source of various secondary metabolites differing in structural characteristic with promising biological activities. Among such is granulatamide B (1), a tryptamine-derived alkaloid, characterized by unsaturated N-fatty acyl moiety, which was found to exhibit high cytotoxicity against various cancer cell lines. Therefore, within the Bioprospecting of the Adriatic Sea project, we have synthesized granulatamide B following the procedure of Fürstner’s Fe-catalyzed synthesis as well as structural analogues by the modification of the side chain (number of C-atoms and saturation degree). Currently, total of 13 compounds have been prepared and examined for antiproliferative and cytotoxic activities applying MTT (3-(4, 5- dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide) assays. Granulatamide B (1) and 9 (analogue with retinoyl moiety) have exerted the most promising, non-selective anticancer activities against SW620, CFPAC-1, MCF-7 and HepG2 cancer cells with determined IC50 values in the range 20-39 µM. Finally, the presented results highlight the importance of the indole skeleton as the pharmacophore group in medicinal chemistry and potential of fatty acids to modulate pharmacological properties of target molecules.

granulatamide B, structural analogues, antiproliferative

nije evidentirano