Alkaloids from marine invertebrates as important leads for anticancer drugs discovery and development.

The present review describes research on novel natural antitumor alkaloids isolated from marine invertebrates. The structure, origin, and confirmed cytotoxic activity of more than 130 novel alkaloids belonging to several structural families (indoles, pyrroles, pyrazines, quinolines, and pyridoacridines), together with some of their synthetic analogs, are illustrated. Recent discoveries concerning the current state of the potential and/or development of some of them as new drugs, as well as the current knowledge regarding their modes of action, are also summarized. A special emphasis is given to the role of marine invertebrate alkaloids as an important source of leads for anticancer drug discovery.

Phallusiasterols A and B: two new sulfated sterols from the Mediterranean tunicate Phallusia fumigata and their effects as modulators of the PXR receptor.

Purification of the apolar extracts of the marine ascidian Phallusia fumigata, afforded two new sulfated sterols, phallusiasterols A (1) and B (2). The structures of the new compounds have been elucidated using mass spectrometry and NMR experiments. The effects of phallusiasterols A and B as modulators of pregnane-X-receptor (PXR) have been investigated. These studies revealed that phallusiasterol A induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target genes CYP3A4 and MDR1 in the same cell line. Molecular docking calculations suggested the theoretical binding mode of phallusiasterol A with hPXR and revealed that phallusiasterol A fitted well in the LBD of PXR.

Meroterpenes from marine invertebrates: structures, occurrence, and ecological implications.

Meroterpenes are widely distributed among marine organisms; they are particularly abundant within brown algae, but other important sources include microorganisms and invertebrates. In the present review the structures and bioactivities of meroterpenes from marine invertebrates, mainly sponges and tunicates, are summarized. More than 300 molecules, often complex and with unique skeletons originating from intra- and inter-molecular cyclizations, and/or rearrangements, are illustrated. The reported syntheses are mentioned. The issue of a potential microbial link to their biosynthesis is also shortly outlined.

Further investigation of the Mediterranean sponge Axinella polypoides: isolation of a new cyclonucleoside and a new betaine.

An exhaustive exploration into the metabolic content of the Mediterranean sponge Axinella-polypoides resulted in the isolation of the new betaine 5 and the new cyclonucleoside 8. The structures of the new metabolites were elucidated by spectroscopic methods assisted by computational methods. The analysis also provided evidence that the sponge does not elaborate pyrrole-imidazole alkaloids (PIAs) but, interestingly, it was shown to contain two already known cyclodipeptides, compounds 9 (verpacamide A) and 10.

New bioactive alkyl sulfates from Mediterranean tunicates.

Chemical investigation of two species of marine ascidians, Aplidium elegans and Ciona edwardsii, collected in Mediterranean area, led to isolation of a series of alkyl sulfates (compounds 1-5) including three new molecules 1-3. Structures of the new metabolites have been elucidated by spectroscopic analysis. Based on previously reported cytotoxic activity of these type of molecules, compounds 1-3 have been tested for their effects on the growth of two cell lines, J774A.1 (BALB/c murine macrophages) and C6 (rat glioma) in vitro. Compounds 1 and 2 induced selective concentration-dependent mortality on J774A.1 cells.