User:Nepa 1013/3- Alkylpyridinium

3- Alkylpyridinium (3-APs) are natural compounds that occur mainly in marine sponges belonging to the order Haplosclerida. These compounds are most interesting as novel potential pharmaceuticals in treating several diseases. 3-APs polymers are potent anticholinesterase agents, in addition, they show hemolytic and cytotoxic activities. More than 70 structurally different 3-APs have been isolated from marine sponges. However, not all such sponges contain 3-AP compounds. Even variation in content of 3-APs has been detected even within a single sponge species collected from different geographical area. Although 3-APs look structurally quite simple, the structure elucidation by NMR spectroscopy is complicated by the fact that most of the methylene groups in the alkyl chains show the same chemical shift. Therefore, the 3-APAs are an ideal test case for a combined approach of NMR spectroscopy and mass spectrometry.

History
The chemical studies on sponges of the order Haplosclerida started in 1978 with the work of Schmitz et al. on different species of the genus Haliclona with the aim to identify the compounds responsible for the high ichthyotoxicity of the aqueous extract of this sponge. They were able to isolate the toxic halitoxin, identified as a complex mixture of 3-alkylpyridinium polymeric salts.

Biological Activities
These compounds exerts large spectrum of biological activity mainly cytotoxicity, ichthyotoxicity, inhibition of bacterial growth, and enzyme inhibition which depend largely on the degree of polymerization. In general, 3-APs monomers, dimers and trimers possess great antimicrobial activity, while higher polymers show more pronounced cytolytic, cytotoxic and antifouling activities. Frequently, only one type of biological assay was carried out for a particular compound. The most widely employed are cytotoxicity assays on different normal or transformed cell lines, or antimicrobial assays.

Cytolytic activity
At present, there are no reports indicating a cytotoxic activity of natural 3-AP monomers and oligomers, and it appears that the ability to permeabilize cells is closely associated with those 3-APs compounds which are polymeric in nature, However, according to the structure of some monomeric and oligomeric alkylpyridines and their structural similarity to certain neutral or cationic surfactants, they might be expected to be cytolytically quite active.

Cytotoxic activity
Almost all 3-APs monomers exert moderate cytotoxicity against certain transformed cell lines in the concentration range of few micrograms per milliliter. Cyclostellerramines and dehydrocyclostellettamines are the examples of cyclic alkylpyridinium compounds that were reported to inhibit muscarinic acetycholine receptors as well as histone deacetylase enzymes.

Antifouling agents
Poly-APS and some other natural 3-alkylpyridines were also found to be very effective in preventing microbial biofilm formation. Preliminary tests have confirmed that some monomeric and oligomeric synthetic analogues of poly-APS also exert antifouling activity, which makes these compounds promising candidates as new environmentally-friendly ingredients in the new generation of antifouling coatings.

Potential use of 3- Alkylpyridinium compounds
3- APs compounds possess a plethora of biological activities that might be of certain interest in some application such as antitumor drugs, transfection agents or components in antifouling paints. There are currently no reports if such applications for 3- AP monomers and oligomers, but some progress had been recently made in studying the possible use of polymeric 3-APs.