Estudos in silico visando aplicação farmacológica de cafeatos monoterpênicos idealizados ; In silico studies aiming pharmacological application of idealized monoterpenic cafeates

Caffeic acid is a natural compound belonging to the phenylpropanoid class that has different pharmacological properties. Thus, in order to enhance the effects of caffeic acid, we used the molecular hybridization technique of caffeic acid with monoterpenic alcohols, reported in the literature as promising therapeutic agents. Thus, in this study, in silico, in order to reduce costs and time, the pharmacokinetic properties and pharmacological potential of caffeic acid (1), ten monoterpenic alcohols (2-11) and ten idealized monoterpenic cafeates (12-21), resulting from the hybridization of caffeic acid with monoterpenic alcohols: (+)-linalool (2), menthol (3), myrtenol (4), peryl alcohol (5), verbenol (6), cyclohexanol (7), carveol (8), citronellol (9), geraniol (10) and (-)-linalool (11). The molecular and pharmacological properties were evaluated using cheminformatics tools. From the analysis of data obtained from Molinspiration, it can be observed that there was no violation of Lipinski's rule of five, thus, it is likely that the compounds evaluated present good oral bioavailability. Furthermore, Molinspiration indicated pharmacological potential for the compounds, and the results obtained with the Swiss Target Prediction tool indicated that most idealized hybrids significantly pointed to the inhibition of the enzyme 17-beta-dehydrogenase 2. With molecular docking it was observed that all compounds evaluated were anchored in the channel that is the active site of the enzyme. The enzyme has two access slits to the active site and most compounds were closer to the larger slit, which is further away from the active site. Therefore, such interactions may not result in enzymatic inhibition, moreover, it was found that compounds 14 and 19 anchored in the active site of the enzyme, interacting with the amino acid residue Tyr 155, this could be confirmed by the dendrogram generated in the software. The ADMET properties of the compounds were also evaluated, which showed negative results for the P-glycoprotein inhibition ...