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Furanchalcone–biphenyl hybrids: synthesis, in silico studies, antitrypanosomal and cytotoxic activities

  • Elisa García
  • Rodrigo Ochoa
  • Isabel Vásquez
  • Laura Conesa-Milián
  • Miguel Carda
  • Andrés Yepes
  • Iván D. Vélez
  • Sara M. RobledoEmail author
  • Wilson Cardona-GEmail author
Original research
  • 43 Downloads

Abstract

The synthesis, antitrypanosomal, and cytotoxic activities of 17 furanchalcone derivatives are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Eleven compounds were active against amastigotes of T. cruzi with EC50 values lower than 40 µM. Hybrids 7b–7d and 8a–8g showed better activity than benznidazole. Structure activity relationship (SAR) showed that the presence of electron withdrawing groups, such as nitro or fluorine, increased the activity and that the degree of oxygenation is essential for activity. In addition, molecular docking was used to identify a possible protein target for the designed compounds. A spearman correlation of 0.608 between the predicted scores and the experimental data profile the enzyme cruzipain as a potential candidate. Finally, in silico ADMET studies of the arylfuranchalcones showed that these novel compounds have suitable drug-like properties, making them potentially promising agents for antichagasic therapy.

Keywords

Chagas disease Trypanosoma cruzi Furanchalcone Hybrids In silico studies Biphenyl 

Notes

Acknowledgements

The authors thank Universidad de Antioquia (Grants CODI 6203 and CIDEPRO) for financial support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2323_MOESM1_ESM.doc (6.2 mb)
Supplementary Information.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Elisa García
    • 1
  • Rodrigo Ochoa
    • 2
  • Isabel Vásquez
    • 1
  • Laura Conesa-Milián
    • 3
  • Miguel Carda
    • 3
  • Andrés Yepes
    • 1
  • Iván D. Vélez
    • 2
  • Sara M. Robledo
    • 2
    Email author
  • Wilson Cardona-G
    • 1
    Email author
  1. 1.Química de Plantas Colombianas, Institute of ChemistryFaculty of Exact and Natural Sciences, University of Antioquia-UdeAMedellínColombia
  2. 2.PECET-Medical Research Institute, Faculty of MedicineUniversity of Antioquia-UdeA. Calle 70MedellínColombia
  3. 3.Department of Inorganic and Organic ChemistryJaume I UniversityCastellónSpain

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