Design, Synthesis, Trypanocidal Activity, and Studies on Human Album in Interaction of Novel S-Alkyl-1,2,4-triazoles

• Published in: Journal of the Brazilian Chemical Society Vol. 30; no. 7; pp. 1378 - 1394
• Main Authors: Franklim, Tatiany N., Freire-de-Lima, Leonardo, Chaves, Otávio A., LaRocque-de-Freitas, Isabel F., Silva-Trindade, Joana D. da, Netto-Ferreira, José C., Freire-de-Lima, Célio G., Decoté-Ricardo, Debora, Previato, José O., Mendonça-Previato, Lucia, Lima, Marco E. F. de
• Format: Journal Article
• Language: Portuguese
• Published: Sociedade Brasileira de Química 01-07-2019
• Subjects: CHEMISTRY, MULTIDISCIPLINARY; 1,2,4-triazole-3-thioether; molecular hybridization; piperine; human serum albumin; Trypanosoma cruzi
• ISSN: 1678-4790
• DOI: 10.21577/0103-5053.20190033

Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 µmol L-1, respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream.