Trypanocidal Activity of Flavanone Derivatives

Abstract

Chagas disease, also known as American trypanosomiasis, is classified as a neglected disease by the World Health Organization. For clinical treatment, only two drugs have been on the market, Benznidazole and Nifurtimox, both of which are recommended for use in the acute phase but present low cure rates in the chronic phase. Furthermore, strong side effects may result in discontinuation of this treatment. Faced with this situation, we report the synthesis and trypanocidal activity of 3-benzoyl-flavanones. Novel 3-benzoyl-flavanone derivatives were prepared in satisfactory yields in the 3-step synthetic procedure. According to recommended guidelines, the whole cell-based screening methodology was utilized that allowed for the simultaneous use of both parasite forms responsible for human infection. The majority of the tested compounds displayed promising anti-Trypanosoma cruzi activity and the most potent flavanone bearing a nitrofuran moiety was more potent than the reference drug, Benznidazole.

In Vitro Evaluation of Arylsulfonamide Derivatives against Trypanosoma cruzi

“…Thus, with the target compounds in hand, in vitro bioassays using trypomastigote and amastigote forms of Y-strain T. cruzi of β-galactosidase transfected the Tulahuen strain of T. cruzi. The whole cell-based approach is an ideal screening methodology given that it enables the evaluation of bioactive compounds against anti T. cruzi activity in infected cells whilst simultaneously monitoring their effects on both amastigotes and trypomastigotes in the same system [20][21][22][23]. Benznidazole was used as a positive control against T. cruzi (IC 50 = 3.81 µM, CC 50 = 2381 µM, and SI = 625) and cytotoxicity was determined in mammalian L929 cells (Table 1).…”

A comprehensive review on potential candidates for the treatment of chagas disease

“…The whole cell-based screening method was applied in accordance with established guidelines, enabling the simultaneous use of both T. cruzi parasite types that cause human infection. The majority of the substances tested showed positive anti-T. cruzi activity, with the most potent flavanone, which has a nitrofuran moiety, surpassing the reference drug, benznidazole, which had an IC 50 value of 3.8 M. (Maciel Diogo et al, 2020). were found to be highly effective than the control drug benznidazole (IC 50 14.6 μM).…”

Crossing borders: On‐Water Synthesis of Flavanones

“…antibacterial [25,26] among others, they are considered privileged structures [3] . Some relevant examples of flavanones with biological activities are shown in Figure 1 [27–31] …”