Síntese e avaliação do potencial biológico de 1,2,3-triazóis derivados da zidovudina e ésteres graxos

Abstract

Functionalized triazoles are organic substances that have a wide synthetic and pharmacological potential. The present work is divided into two parts, where the results of the synthesis and evaluation of the biological potential of the derivatives were reported: 1,2,3-triazoyl-zidovudine and 1,2,3-triazoyl-fatty esters. Firstly, the results of the 1,2,3-triazoyl-zidovudine study were addressed. The Chapter 1 describes the use of an organocatalytic system consisting of zidovudine (0.3 mmol) 1, α-substituted ketones, (0.36 mmol) 2a-p, 1,8-diazabicyclo[5.4.0]undec-7-ene (10 mol%) as an organocatalyst and dimethylsulfoxide as a solvent at 70 °C for 24 h. Sixteen 1H-1,2,3- triazole-zidovudine 3a-p were obtained (Scheme A) with excellent yields (59%-91%). Scheme 1 In order to investigate the antioxidant capacity of the molecules, the in vitro experiments of reactive species assay and removal of species reactive to thiobarbituric acid were carried out, which the molecules that showed antioxidant activity in lower concentrations were 3a, 3k, 3f and 3h (Scheme 2). Scheme 2 Therefore, the results of the study 1,2,3-triazoyl-fatty esters were addressed. The Chapter 2 describes the use of 1,8-diazabicyclo[5.4.0]undec-7-ene (5 mol%) as anorganocatalyst for 1,3-dipolar cycloaddition of fatty esters (0.2 mmol) 4a-c with aryl azides (0.3 mmol) 5a-j. Through enolate-mediated organocatalysis, the reactions were conducted at 70 °C for 3-6 hours, using dimethylsulfoxide as solvent. In these reaction conditions, twelve 1H-1,2,3-triazoles derived from 6a-l fatty esters (Scheme 3) were obtained with moderate to excellent yields, ranging from 35% to 99%. Scheme 3 All compounds of the palmitic acetoacetate triazole class were evaluated for cytotoxic activity against human bladder cancer cells by the in vitro tetrazolium salt reduction assay and compounds 6a, 6d, 6e and 6g were identified as the most promising. They stood out for presenting the lowest IC50 inhibitory concentration (Scheme 4): 8.72 μM (6d), 12.74 μM (6g), 18.65 μM (6e) and 22.50 μM (6a). Scheme 4