ABSTRACT
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.
Subject(s)
Alkaloids/chemistry , Antineoplastic Agents/chemistry , Aquatic Organisms/chemistry , Drug Discovery , Invertebrates/chemistry , Alkaloids/pharmacology , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Biological Products/chemistry , Biological Products/pharmacology , Cyclin-Dependent Kinases/antagonists & inhibitors , Drug Resistance, Neoplasm , Humans , Mitosis/drug effects , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Structure-Activity Relationship , Topoisomerase I Inhibitors/chemistry , Topoisomerase I Inhibitors/pharmacologyABSTRACT
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.
Subject(s)
Cholestanol/analogs & derivatives , Receptors, Steroid/drug effects , Sulfuric Acid Esters/pharmacology , Urochordata/metabolism , ATP Binding Cassette Transporter, Subfamily B/genetics , Animals , Cholestanol/chemistry , Cholestanol/isolation & purification , Cholestanol/pharmacology , Cytochrome P-450 CYP3A/genetics , Gene Expression Regulation/drug effects , Hep G2 Cells , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mediterranean Sea , Molecular Docking Simulation , Pregnane X Receptor , Receptors, Steroid/metabolism , Sterols/chemistry , Sterols/isolation & purification , Sterols/pharmacology , Sulfuric Acid Esters/chemistry , Sulfuric Acid Esters/isolation & purificationABSTRACT
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.
Subject(s)
Aquatic Organisms/chemistry , Invertebrates/chemistry , Terpenes/pharmacology , Animals , Humans , Oceans and Seas , Porifera/chemistry , Terpenes/chemistry , Terpenes/isolation & purification , Urochordata/chemistryABSTRACT
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.
Subject(s)
Axinella/chemistry , Betaine/chemistry , Nucleosides/chemistry , Peptides, Cyclic/chemistry , Animals , Betaine/isolation & purification , Mediterranean Sea , Nucleosides/isolation & purification , Peptides, Cyclic/isolation & purification , Spectrum AnalysisABSTRACT
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.
