Marialuisa Menna

Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites

In the present study, 13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau’amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas genera have been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau’amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds. In addition, evaluation of the activity of the test alkaloids (2–14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids.

Chemical Diversity of Bioactive Marine Natural Products: An Illustrative Case Study

The marine environment contains a number of plants, animals and micro organisms, which, due to the unique adaptations to their habitat, elaborate a wide diversity of natural products with specific bioactivities. These products provide a rich source of chemical diversity that can be used to design and develop new potentially useful therapeutic agents. The huge variety of the structures present in marine organisms has been illustrated through the case study of the sponge Plakortis simplex, whose chemical analysis, started in our laboratories about ten years ago, revealed an incredible variety and abundance of secondary metabolites. The obtained results have been presented with the intention of drawing some conclusions of general relevance. Particularly, the problem of the limited availability of natural compounds for both structural and preliminary pharmacological studies has been discussed, this issue becoming a serious obstacle when the pharmacological research reaches a more advanced stage. Furthermore, the origin of the chemodiversity in Plakortis simplex and, in general, in marine invertebrates has been discussed; in this respect, the possible cooperative role of symbiotic micro-organisms in the biosynthesis of the varied metabolic content typical of these organisms has been considered.

New cytotoxic steroids from the marine sponge Dysidea fragilis coming from the lagoon of Venice

The sterol composition of the sponge Dysidea fragilis, coming from the lagoon of Venice, has been investigated; our results confirmed the variability of D. fragilis biochemistry. The sponge elaborates, in addition to eight usual 3 beta-hydroxy sterols, thirteen polyhydroxysterols, eight of them (6-13) were novel compounds. Their structures were established by spectroscopic data. New compounds 3 beta,5 alpha,6 beta,7 alpha-tetrahydroxy-cholest-8(9)-en-11-one (8), 3 beta,5 alpha,6 alpha-trihydroxy-9,11-secocholest-7-en-9-one (9) and 3 beta,5 alpha,6 alpha,9 alpha-tetrahydroxy-cholest-7-ene-6-sulfate (11) were proved to be cytotoxic on two different tumor cell lines in vitro.

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.

Alkaloids from Marine Ascidians

About 300 alkaloid structures isolated from marine ascidians are discussed in term of their occurrence, structural type and reported pharmacological activity. Some major groups (e.g., the lamellarins and the ecteinascidins) are discussed in detail, highlighting their potential as therapeutic agents for the treatment of cancer or viral infections.

Five new polar sterols from the black coral Antipathes subpinnata

In addition to the known (20S,22E)-cholesta-1,4,22-triene-16 beta,18, 20-triol-3-one, (20S,22E)-24-methyl-cholesta-1,4,22-triene-16 beta,18,20-triol-3-one, and (20S,22E)-24-methylcholesta-4,22-diene-16 beta,18,20-triol-3-one, the methanol extract of the Mediterranean anthozoan Antipathes subpinnata was shown to contain five new sterols: (20S,22E)-cholesta-1,4,22-triene-18,20-diol-3-one, (20S,22E)-24-methylcholesta-1,4,22-triene-18,20-diol-3-one, (20S)-cholest-4-ene-16 beta,18,20-triol-3-one, (20S,22E)-cholesta-4,22-diene- 16 beta,18,20-triol-3-one, and (20S,22E)-24-methylcholesta-4,22-diene-16 beta,18,20-triol-3-one, whose stereostructures were elucidated on the basis of physicochemical evidence. The previously unassigned chirality at C-20 of the known sterols has been also established as S.

Aplidiasterols A and B, two new cytotoxic 9,11-secosterols from the Mediterranean ascidian Aplidium conicum.

Two novel 9,11-secosterols, aplidiasterols A (3beta,6beta,11-trihydroxy-9,11-seco-5alpha-cholest-7-en-9-one, 1) and B (3beta,5alpha,6beta,11-tetrahydroxy-9,11-secocholest-7-en-9-one, 2), along with the known secosterols 3 and 4, were isolated from the Mediterranean ascidian Aplidium conicum and their structures were determined by spectroscopic data. Aplidiasterols A and B were found to be cytotoxic against rat glioma (C6) and murine monocyte/macrophage (J774) tumor cells in vitro. Compounds 1-4 represent the first example of secosterols isolated from tunicates.

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.

Polyaxibetaine, an amino acid derivative from the marine sponge Axinella polypoides.

A new pyridinium derivative, polyaxibetaine (3), has been isolated from the marine sponge Axinella polypoides, together with two known modified amino acids, 1 and 2. The planar structure of compound 3 has been elucidated by spectroscopic methods; definition of the absolute configuration of compounds 1-3 has been carried out through ECD studies.

Novel antiproliferative alkyl sulfates from the Mediterranean tunicate Ascidia mentula

Abstract A bioassay guided approach was used to isolate two antiproliferative sulfated metabolites, the 3,7,11,15-tetramethyl-hexadecan-1,19-sodium disulfate (1a) and the heneicosane-1,21-sodium disulfate (2a) from the Mediterranean tunicate Ascidia mentula. Their structures were determined by an extensive spectroscopic analysis and chemical methods.