Estudo semiempirico da inibição da enzima AChE por policetídeos extraídos da esponja marinha Plakortis angulospiculatus

Abstract

The Evil of Alzheimer is a disease neurodegenerativa that reaches to the cognitive functions among them the memory, attention and learning. The main strategy used for his/her treatment is addressed in the search of improving the hipofunção colinérgica, inhibiting the enzyme acetylcholinesterase, so that the acetylcholine can stay more available in the rift sináptica for the accomplishments of the sinapses, since this enzyme has the hidrolisar function the acetylcholine. The nature offers an enormous variety of substances used as fármacos and the sea sponges has been demonstrating be rich in these substances. They were extracted of the sponge Plakortis angulospiculatus three polyketides that through the method Ellman demonstrated activity anticolinesterásica. Through techniques of Molecular Modelling, calculations semiempiricos were accomplished using the method PM3 to analyze the geometric interactions and energies involved in the compound polyketidesacetylcholinesterase with the objective of analyzing a possible use of these as fármacos for the Evil of Alzheimer. As if he/she didn't know the state in that the ranch would be (with Ser200 and neutral His440 or no) in the moment of the interaction, calculations were accomplished for the three polyketides in both ranches. Studies with inhibitors already known tacrina and huprina X (both neutral one and protonadas) they were also accomplished at both ranches in order to comparison. Resulted obtained he in this work showed the reliability of the employed method, likewise as values of favorable entalpia for the formation of all the compounds independent pollyketide-acetylcholinesterase of the ranch. It was observed by the energy values a preference when the same ones if they found in the ranch protonado diferencialmente of the inhibitors tacrina and huprina X that independent of his/her state (protonados or no) they showed better interaction for the neutral ranch. The calculations accomplished for the tacrina demonstrated that even after optimization the main interactions described already by the literature stayed and that possibly she meets protonada inside of the seen ranch the values of energy found for this structure. The huprina X that is a hybrid of the tacrina with the huperzina A it showed HER likewise the most significant interactions as the more favorable energy values, what is in agreement with the high constant of inhibition of 26pM found in the literature for human's acetilcolinesterase. Before the obtained data we can end that the polyketides in spite of they obtain favorable energy values the formation of the compound polyketide-acetylcholinesterase these values are not competitive with the energy values found for the inhibitors tacrina and huprina X. however, in the production of a fármaco they are not taken into account just energy interactions and as the tacrina it already demonstrated to possess high hepatic toxicity, besides adverse reactions as nausea and vomit, the polyketides for they be natural substance were able to in this case be competitive if they demonstrated to possess softer adverse reactions.