Anti-Proliferative Potential of Secondary Metabolites from the Marine Sponge sp.: Moving from Correlation toward Causation.

Marine sponges have been recognized as a rich source of potential anti-proliferative metabolites. Currently, there are two sponge-derived anti-cancer agents (a macrolide and a nucleoside) isolated from the Porifera phylum, suggesting the great potential of this sponge as a rich source for anti-neoplastic agents. To search for more bioactive metabolites from this phylum, we examined the EtOAc extract of sp. sponge. We isolated seven compounds (-), including four 4-methylene sterols (-), two nucleosides ( and ), and one macrolide (). Among them, theonellasterol L () was identified for the first time, while 5'--acetyl-2'-deoxyuridine () and 5'--acetylthymidine () were the first identified deoxyuridine and thymidine derivatives from the sponge sp. These structures were elucidated based on their spectroscopic data. The anti-proliferation activity of compounds - against the MCF-7, MDA-MB-231, T-47D, HCT-116, DLD-1, K562, and Molt 4 cancer cell lines was determined. The results indicated that the 14-/15-oxygenated moiety played an important role in the antiproliferative activity and the macrolide derivatives dominated the anti-proliferative effect of the sponge sp. The in silico analysis, using a chemical global positioning system for natural products (ChemGPS-NP), indicated an anti-proliferative mode of actions (MOA) suggesting the potential applications of the isolated active metabolites as anti-proliferative agents.