The worldwide emergence of viral diseases such as Zika, Dengue, Chikungunya, West Nile and Yellow Fever urge the search for solutions to eliminate their common vector, the Aedes aegypti mosquito. This paper describes the quantitative structure-activity relationship (QSAR) and docking studies of a series of nine 3-(3-aryl-1,2,4-oxadiazol-5-yl)propionic acids (AOPA), 1-9, previously published by our group. Additionally, three new 1,2,4-oxadiazoles, 10-12, have also been synthesized, characterized and studied. The QSAR and docking studies of all compounds, 1-12, clearly indicate that larger hydrophobic substituents such as biphenyl groups attached on position 3 in 1,2,4-oxadiazoles improve the larvicidal activity. It is worthwhile to mention that nanocapsulation of compounds 10-12 were necessary to help their dissolution in water and these three new 1,2,4-oxadiazoles also exhibited approximately equal or higher larvicidal activities compared to the former prototypes at stage L4.

Diabetes is a chronic metabolic disorder characterized by insufficient insulin production, the cells’ inability to use this insulin, or a combination of both, leading to secondary complications such as diabetic neuropathy and retinopathy. One way to prevent or control such complications is the use of aldose reductase (AR) inhibitors. In this work, we synthesized and tested new candidates for human AR inhibition containing a 2-thiopyrimidin-4-one heterocycle as a central ring. The fifteen derivatives were tested in vitro and their binding modes were evaluated via molecular docking simulations. AR inhibition assays showed that all synthesized compounds were able to inhibit the AR enzyme at 50 μM. From these results, seven compounds were noteworthy and had their half maximal inhibitory concentration (IC50) values estimated, ranging from 2.0 to 14.5 μM. Molecular docking simulations showed that these compounds bind specifically to the catalytic subpocket and the results indicate a good association between in vitro and in silico studies.

Pyrimidines and their derivatives are present in various biologically active molecules. Most of the synthetic methods employed to achieve the pyrimidinone ring consist of two stages: the synthesis of a Michael intermediate from an aldehyde and an "active methylene" containing compound; and the condensation of this intermediate with a molecule containing an uranium moiety. This may take one to two days of laboratory work. In this paper we describe a new methodology in which these derivatives are obtained via multicomponent synthesis mediated by ultrasound in only 2 hours. In order to obtain water-soluble pyrimidinone derivatives, our previous compounds were further converted into their sodium salts. In pharmacologic studies, these salts inhibited phenylephrine-induced contraction in isolated rat aorta, suggesting that they may act as alpha-1 antagonists and, therefore, are candidates for anti-hypertensive drugs.