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Some important atypical antipsychotic drugs target the serotonergic receptor 2A (5-HT2AR). Currently, new therapeutic strategies are needed to offer faster onset of action with fewer side effects and, therefore, greater efficacy in a substantial proportion of patients with neuropsychological disorders such as Autism and Parkinson. The main objective of this work was to use SBDD methods to identify new hit compounds potentially useful as precursors of novel and selective 5-HT2AR antagonists. A structure-based pharmacophore screening study based on a selective antagonist was carried out in ten databases. The set obtained was refined using molecular docking, and the five most promising compounds were subjected to molecular dynamics simulations. The most stable and promising hit occupied a side pocket present in the 5-HT2AR, a site that can be explored to obtain selective ligands. Simulations against 5-HT2CR and D2R showed that the best hit could not form stable complexes with these targets, strengthening the hypothesis that the hit presents selective binding by the receptor of interest. The selected hits showed some predicted toxicity risk or violated some drug-likeness property. However, it can be concluded that the identified hits are the most promising for performing in vitro assays. Once the presence of activity is confirmed, they could become precursors of optimized and selective antagonists of 5-HT2AR. An SBDD study was carried out to identify new selective 5-HT2AR ligands potentially useful for designing selective atypical antipsychotics. [ABSTRACT FROM AUTHOR]

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The Ferreira-Kiralj hydrophobicity parameter Wc is a number fraction of hydrophobic carbon atoms and can be regarded as a constitutional descriptor since its calculation depends only on the number of polar and nonpolar carbons in a compound. Hydrophobicity is important to the toxicity of ionic liquids (ILs), which are salts by nature. Herein, a descriptor for this property was calculated using a simple adaptation of the type of polar carbon atoms included (WcAdap) to explore the possibility of its use in quantitative structure-activity relationship (QSAR) studies of ILs. The resulting model was tested using a database of ILs with toxicity against the Leukemia rat cell line IPC-81. Two other models were constructed using Crippen log P and Mannhold log P descriptors, which are both available in the free program PaDEL. The use of WcAdap led to a better and more indicative model. Thus, WcAdap may be a suitable molecular descriptor for the hydrophobicity of ILs in QSAR studies.

Dipyrone is an antipyretic and analgesic medicine very used by the Brazilian population. The administration is considered safe even in pregnant women, nurseling and children, but is forbidden in some countries, as supposedly causes agranulocytosis and aplastic anemia. In 2001, National Health Surveillance Agency (Anvisa) approved the commercialization of this medicine in Brazil. However, it does not matter the safeness in the use of a medicine advances, if it does not have quality. Based on this quality, this work was elaborated, that analyzes seven samples of commercialized different marks of dipyrone oral solution in pharmaceutical establishment in the Cascavel city, Paraná, Brazil. The results demonstrate that the quality control of similar drugs must be improved as were the ones that presented quality deviations.