Synthesis and Evaluation of Antibacterial Activity of 1,2,3-Triazole and Ether Derivatives of Paeonol

Author(s)

Laura Patricia R. Figueroa ^[1] ; Nayara A. dos Santos ^[2] ; Pedro Henrique O. Santiago ^[3] ; Wanderson Romão ^[4] ; Valdemar Lacerda Junior ^[5] ; Javier Ellena ^[6] ; Ana Camila Micheletti ^[7] ; Warley S. Borges ^[8]

Affiliation

^[1] Universidade Federal do Espírito Santo. Departamento de Química. Programa de Pós-Graduação em Química - Brasil

^[2] Universidade Federal do Espírito Santo. Departamento de Química. Programa de Pós-Graduação em Química - Brasil

^[3] Universidade de São Paulo. Instituto de Física de São Carlos - Brasil

^[4] Universidade Federal do Espírito Santo. Departamento de Química. Programa de Pós-Graduação em Química - Brasil

^[5] Universidade Federal do Espírito Santo. Departamento de Química. Programa de Pós-Graduação em Química - Brasil

^[6] Universidade de São Paulo. Instituto de Física de São Carlos - Brasil

^[7] Universidade Federal de Mato Grosso do Sul. Instituto de Química - Brasil

^[8] Universidade Federal do Espírito Santo. Departamento de Química. Programa de Pós-Graduação em Química - Brasil

• Document type: Journal article
• Source: Journal of the Brazilian Chemical Society; v. 34, n. 1, p. 25-35, 2023-01-06.

Abstract

Multi-drug-resistant bacteria (MDR) are the cause of different infections and diseases that have affected humanity for a long time, and have been an emerging global health problem that has led to increased morbidity and mortality. The growing emergence of MDR bacteria has underlined the need for development and discovery of new antibacterial compounds. In this context, a series of new paeonol 1,2,3-triazole and ether derivatives were synthesized using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and nucleophilic substitution. Paeonol has been a natural product widely studied due to its many biological activities, as well as its derivatives. Three ether derivatives (two unpublished) and ten triazole derivatives (six unpublished) of paeonol were obtained, which were determined by nuclear magnetic resonance (NMR), Fourier transform infrared spectrometry (FTIR), Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and six of them by X-rays, which is the first study of this type presented for these compounds. All the synthesized compounds were evaluated as antibacterial agents against Staphylococcus aureus and Escherichia coli, obtaining a minimum inhibitory concentration (MIC) above 100 µg mL-1. The results showed that CuAAC and nucleophilic substitution were very useful to obtain new paeonol triazole and ether derivatives and the products were obtained in yields from 21.3 to 98.5%. The advantages of these reactions (high yield in most compounds, reaction time, low impurities) show that using the method to produce new derivatives is advisable thus assisting in the discovery of new potential bioactive compounds. (AU)

• FAPESP's process: 17/15850-0 - X-ray diffraction as a tool in potential drug development
• Grantee: Eduardo Ernesto Castellano
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/10066-5 - Crystallographic and structural study of new substances with potential biological activities
• Grantee: Pedro Henrique de Oliveira Santiago
• Support Opportunities: Scholarships in Brazil - Post-Doctoral