Elongation on Aliphatic Chain Improves Selectivity of 2-Hydroxy-3,4,6-Trimethoxyphenyl Chalcone on Trypanosoma Cruzi

Abstract

Aim: Our objective was to investigate the trypanocidal effect of the chalcone (2E,4E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-5-phenylpenta-2,4-dien-1-one (CPNC). Material & methods: Cytotoxicity toward LLC-MK2 host cells was assessed by MTT assay, and the effect on Trypanosoma cruzi life forms (epimastigotes, trypomastigotes and amastigotes) was evaluated by counting. Flow cytometry analysis was performed to evaluate the possible mechanisms of action. Finally, molecular docking simulations were performed to evaluate interactions between CPNC and T. cruzi enzymes. Results: CPNC showed activity against epimastigote, trypomastigote and amastigote life forms, induced membrane damage, increased cytoplasmic reactive oxygen species and mitochondrial dysfunction on T. cruzi. Regarding molecular docking, CPNC interacted with both trypanothione reductase and TcCr enzymes. Conclusion: CPNC presented a trypanocidal effect, and its effect is related to oxidative stress, mitochondrial impairment and necrosis.

Graphical abstract

Keywords::

• Chagas disease
• chalcone
• parasitology
• selectivity
• trypanocidal effect

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.future-science.com/doi/suppl/10.4155/fmc-2023-0177

Financial disclosure

The authors are grateful for institutional support from the Northeastern Center for the Application and Use of Nuclear Magnetic Resonance (CENAUREMN) and the National Center of High Performance Processing (CENAPAD-UFC). H Silva dos Santos acknowledges financial support from CNPq (grant no. 306008/2022-0). A Martins acknowledges financial support from CNPq (grant no. 306614/2019-7). M Marinho acknowledges financial support from PDCTR (CNPq/FUNCAP; grant nos. DCT-0182-00048.02.00/21 and 04879791/2022). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors are grateful for institutional support from the Northeastern Center for the Application and Use of Nuclear Magnetic Resonance (CENAUREMN) and the National Center of High Performance Processing (CENAPAD-UFC). H Silva dos Santos acknowledges financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq (grant no. 306008/2022-0). A Martins acknowledges financial support from CNPq (grant no. 306614/2019-7). M Marinho acknowledges financial support from PDCTR (CNPq/Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico FUNCAP; grant nos. DCT-0182-00048.02.00/21 and 04879791/2022). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.