Analysis Of ESI-MS And Structure-activity Relationships Of Inhibitory Activity On Acetylcholinesterase Of Marine Natural Products

The particularity of the ocean environment （high salt, high pressure, lowtemperature and oligotrophic and so on） create the unique living environment ofmarine organisms. And then, their metabolic pathways are special and complex so thesecondary metabolites isolated are new or unique, as well as they usually possesskinds of bioactivities. Almost1000new natural products are reported annual, amongthem half are derived from sponges, corals and the microorganisms isolated fromthem.MS is important for the identification of the marine natural products, and the usualmethods include EI-MS, FAB-MS, MALDI-MS and ESI-MS. Among these methodsthe ESI-MS is widely used in the field of natural products because that this method israpid, accurate and high efficient.There are101natural products from ponges, corals and the microorganismsisolated from them analyzed by using electrospray ionization mass spectrometry（ESI-MS） in order to find out some laws about quasi-molecular ions of these usualmarine natural products and provide reference for future work that how to choose themode for different kinds of structure type of compounds and how to use ESI-MS toscreen the types of the compounds.Through the results, some laws are summaried. The compounds with basic groupsare fit to the positive mode, and those with acid groups are fit to the negative mode ingenerally. Some types e.g. steroids, steroidal saponins, and terpenes are fit to thepattern of ESI （+）, in this pattern the quasi-molecular ions of [M+H]⁺,[M-H₂O+H]⁺,[M+Na]⁺,[M+K]⁺,[2M+H]⁺,[2M+Na]⁺,[2M+K]⁺are common. However, someother types, xanthone, cyclic peptide, lactone and glycerylether, for example, areusually analyzed in the pattern of ESI （–）, and in this pattern the quasi-molecular ionsof [M-H]-and [2M-H]-are in existence. In theory, the compounds with both basic andacid groups can be ionized in the two modes, chromone with multiple carbonyls andhydroxyls can be ionized in these two modes. While some compounds without polar groups can’t be ionized by ESI, also some sompounds can’t be ionized by ESI-MSalthough they contain polar groups, the steroids with multiple hydroxyls but withoutcarbonyls are not fit to ESI-MS, because that their solublensss are weak.At the same time, the approaches contained exploration of isotopic peak,HR-ESI-MS, tandem mass spectrum （MSn）, as well as the announcements in theprocess of ESI-MS are explored. When the compound contains Cl, then the isotopicpeak with the abundance ratio3:1meanwhile the mass to charge ratio has2differences will be existing, similarly, when contains Br, the isotopic peak with theabundance ratio1:1meanwhile the mass to charge ratio has2differences will appear.HR-ESI-MS is useful for structure confirmation more efficiently and it can offerinformation containing the concentration at one point and the abundance in thismoment and so on. The MSncan evidence structure segments the tested samplecontainning more definitely thus improve the accuracy of structure. The analysisresult about ESI-MS will be influenced by many factors containing sample’ solubilityand sample size and so on.Another job of this study is that115natural products and21derivatives of biphenylether were screened in order to test whether these compounds can inhibit the activityof Acetylcholinesterase （AChE） or not. The structure type and structural features ofactive compounds can be summarized by the structure-activity relationship, and thisjob aimed at providing lessons for screening of AChE inhibitors from marine naturalproducts.After the experiment,57compounds showed the inhibition. The structure types ofthe active compounds include citrinin, anthraquinone, steroids, sesquiterpene,isocoumarin, lactone, alkaloid, benzaldehyde derivatives and peptide and so on. Therewere4compounds with moderate or week activities, and their IC50value for AChEare78,42,23, and166μM, respectively.The activity of hydrogenated anthraquinone was stronger than the aromatic one,and the hydroxyl groups at C-4will reduce the activity greatly, and the side chain atC-3had effection on the activity, the longer the side chain was the stronger theactivity was. For citrinin the dimer ones’ activities were stronger than the single ones,and the formic ether group at C-2’ will weaken the activity. When isocoumarincontained long side chain, its activity will be stronger, and aromatization at C-3andC-4will reduce the activity strongly.The experiment and the relevant literature gave us some conclusion that the active compounds have some characteristics, for instance, they always contain nitrogen atom,possess hydrophobic side chain, and they belong to small molecular compounds andso on. Besides, the dynanmics of the activity were influenced by many factors, forexample the length and steric configuration of the side chain, the site of the keysubstitute groups, and the site of double bond.