Síntese organocatalítica de novos 1,2,3-triazóis com potencial interação com DNA : estudos com derivados de tiazolidina e piridina

Abstract

This doctoral thesis describes two methods for synthesizing 1,4,5- trisubstituted 1,2,3-triazoles functionalized with either a thiazolidine or a pyridine unit, both utilizing organocatalysis. The first approach focused on the synthesis of 1,2,3-triazoles containing the thiazolidine unit. To achieve this, organic azides were reacted with a β-keto ester containing the thiazolidine unit using diethylamine (Et₂NH) as a catalyst (10 mol%) and DMSO as the solvent, under 75 °C for 24 hours. As a result, twelve molecules were obtained in yields ranging from 23% to 96%. In addition to the synthesis and characterization of all compounds, molecular docking studies were conducted to evaluate potential interactions with DNA structures. These studies showed that all tested molecules exhibited significant interactions with DNA. Notably, compounds with substituents o-NO₂, o-SC₆H₅, and o-SeC₆H₅ in the azide unit presented DNA interaction score values of -8.3 kcal/mol, -8.2 kcal/mol, and -8.6 kcal/mol, respectively. The second part of this doctoral thesis focused on synthesizing 1,2,3- triazoles containing a pyridine unit. In this case, different organic azides were reacted with α-2-pyridyl-acetophenones using 1,8-Diazabicyclo[5.4.0]undec-7- ene (DBU) as a catalyst (5 mol%) and DMSO as the solvent, at 50 °C for 24 hours. This method led to twenty-three molecules, in yields ranging from 17% to 90%. Furthermore, molecular docking studies demonstrated the relevance of the synthesized molecules, as all compounds exhibited interactions with DNA structures. Particularly, compounds with substituents m-NO2 and 7-chloroquinoline in the organic azide presented DNA interaction score values of -9.3 kcal/mol, and -9.4 kcal/mol, respectively.