Synthesis, Structural Elucidation and Trypanocidal Activity of 2-thiocyanil-1,4-naphthoquinone

Abstract

Aims: This work describes the synthesis of 2-thiocyanil-1,4-naphthoquinone and evaluates its trypanocidal activity. Study Design: Synthesis was carried under conventional heating, microwave and ultrasound irradiation. Molecular modeling was employed to assign correctly the thiocyanil group upon the structure, the quinone was tested against Trypanossoma cruzi. Place and Duration of Study: Synthesis: Department of Chemistry, IFRJ-Campus Rio de Janeiro; Trypanocidal Activity: Department of Biotechnology, IFRJ-Campus Rio de Janeiro, Molecular Modeling: Walter Mors Institute for Research on Natural Products UFRJ-Rio de Janeiro; between June 2015 and July 2017. Methodology: The syntheses were performed under conventional conditions, ultrasound and microwave irradiation. The trypanocidal activity of the 2-thiocyanil-1,4-naphthoquinone was evaluated against epimastigote form and expressed as IC50 value, corresponding to the concentration that causes lysis of 50% of the parasites. Relative IC50 value was obtained by non-linear regression method. The ¹³C NMR shielding constants (σ) were calculated, taking into account Boltzmann statistics, by a gauge including atomic orbital-hybrid density functional theory (GIAO-HDFT) calculation procedure, previously published by some of us. Results: The microwave irradiation was the most efficient method to synthetize the 2-thiocyanil-1,4-naphthoquinone. This compound showed high activity against Trypanosoma cruzi with a IC50 3.27 ± 2.2. The structure was correctly assigned with molecular modeling support. Conclusion: In conclusion, 2- thiocyanil-1,4-naphthoquinone was efficiently synthesized in this work and its trypanocidal activity justify further in vivo studies.