Antichagasic evaluation, molecular docking and ADMET properties of the chalcone (2E)-3-(2-fluorophenyl)-1-(2-hydroxy- 3,4,6-trimethoxyphenyl)prop-2-en-1-one against Trypanosoma cruzi

Abstract

Characterized as a neglected disease, Chagas disease is an infection that, in the current scenario, affects about 8 million people per year, with a higher incidence in underdeveloped countries, Chagas is responsible for physiological disabilities that result in impacts that are slightly reflected in world socioeconomic stability. Although treatments are based on drugs such as Benznidazole, the pathology lacks a continuous treatment method with low toxicological incidence. The present study estimates the anti-chagasic activity of the synthetic chalcone CPN2F based on the alignment between in vitro tests and structural classification in silico studies, molecular docking and ADMET studies. The in vitro tests showed a reduction in the protozoan metabolism in host cells (LLC-MK2). At the same time, the molecular docking models evaluate this growth inhibition through the synergistic effect associated with Benznida- zole against validated therapeutic target key stages (Cruzaine TcGAPDH and Trypanothione reductase) of the Trypanosoma cruzi development cycle. The in silico prediction results reveal an alignment between pharmacokinetic attributes, such as renal absorption and release, which allow the preparation of CPN2F as an antichagasic drug with a low incidence of organic toxicity.

Communicated by Ramaswamy H. Sarma

Keywords:

• T. cruzi
• citotoxic activity
• molecular docking
• in silico study
• Synthetic chalcone

Acknowledgements

The authors thank the Northeastern Center for the Application and Use of Nuclear Magnetic Resonance (CENAUREMN), and Centro Nacional de Processamento de Alto Desempenho (CENAPAD) of the Federal University of Ceara (UFC) for providing computational resources.

Disclosure Statement

There are no conflicts to declare.

Additional information

Funding

We acknowledge financial support from FUNCAP, CNPq and CAPES. Hélcio S. dos Santos acknowledges financial support from the PQ/FUNCAP (Grant#: BP4-0172- 00075.01.00/20). Alexandre M. R. Teixeira also acknowledges financial support from the PQ/CNPq (Grant#: 308178/2021-1).