Desenvolvimento racional de um candidato a fármaco: estudos in sílico, síntese, caracterização e avaliação biológica de um composto contendo o grupamento farmacofórico aceptor de Michael.

Abstract

Technology has been essential in the drug planning process, as it enables the optimization of time and operating costs, but even with all this technology, the search for drugs is a rather difficult task. Medicinal chemistry is the area that reconciles countless other areas during the drug development process. Associated with this, the growing number of cases resulting from endemic diseases, has been encouraging the government to invest in research for the development of compounds to be used in their treatment. Faced with this, a class of molecules that has attracted the scientific community are carbohydrates, molecules with numerous pharmacological and biological activities. Thus, the objective of this work was to sketch the molecular architecture of four drug candidates and evaluate their pharmacokinetic, pharmacodynamic and toxicological properties with the aid of in silico tools, then synthesize the most promising candidate and evaluate their toxicity by in vitro methods. using the Artemia salina Leach microcrustacean and Aedes aegypti mosquito larvae. After evaluations, it was found that the most promising candidate was prop-2-in-1-yl 2,3-dideoxy-2-enopyranosid-4-ulose (candidate 4), which was synthesized after four reaction steps as follows. of an amorphous white solid in excellent yield (87%). The candidate presented an LC50 of 610.370 μg/mL against the brine shrimp. Already against the larvae of the mosquito Aedes aegypti, the candidate showed no significant toxicity and, therefore, it was found that it has no larvicidal activity against the larvae of Aedes aegypti. In short, the compound showed low toxicity against the brine shrimp, a very promising result, whereas the Aedes aegypti larvae did not show larvicidal activity and in silico methods indicated that the molecule has a low probability of toxic effects. , good characteristics for becoming a good drug, a great potential for oral bioavailability, and a marked activity related to enzyme inhibition.