2. Academic Validation
  3. Structure-activity relationship study of antitrypanosomal chalcone derivatives using multivariate analysis

Structure-activity relationship study of antitrypanosomal chalcone derivatives using multivariate analysis

  • Bioorg Med Chem Lett. 2019 Jun 15;29(12):1459-1462. doi: 10.1016/j.bmcl.2019.04.020.
Kaio S Gomes 1,  Thais A da Costa-Silva 1,  Igor H Oliveira 2,  Andrea M Aguilar 2,  Diogo Oliveira-Silva 2,  Miriam Uemi 2,  Wender A Silva 3,  Lennine R Melo 3,  Carlos Kleber Z Andrade 3,  Andre G Tempone 4,  João L Baldim 5,  João Henrique G Lago 6
Affiliations

Affiliations

  • 1 Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP 09210-580, Brazil.
  • 2 Departamento de Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972-270, Brazil.
  • 3 Instituto de Química, Universidade de Brasília, Brasília, DF 70910-900, Brazil.
  • 4 Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, São Paulo, SP 01246-000, Brazil.
  • 5 Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP 09210-580, Brazil. Electronic address: jotaelebaldim@gmail.com.
  • 6 Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP 09210-580, Brazil. Electronic address: joao.lago@ufabc.edu.br.
PMID: 31000155 DOI: 10.1016/j.bmcl.2019.04.020
Abstract

Chagas disease represents one of several neglected diseases with a reduced number of chemotherapeutical drugs including the highly toxic compounds benznidazole and nifurtimox. In this sense, Natural Products represent an import scaffold for the discovery of new biologically active compounds, in which Chalcones are promising representatives due to their antitrypanosomal potential. In this work, a series of 36 chalcone derivatives were synthesized and tested against trypomastigotes of Trypanosoma cruzi. In addition, a detailed investigation on their molecular features was performed. The obtained results suggest that certain molecular features are fundamental for an efficient antitrypanosomal potential of Chalcones, such as allylic groups, α,β-unsaturated carbonyl system, and aromatic hydroxyl groups. These results were obtained based on the interpretation of machine-learning and multivariate statistical methods, which revealed the essential characteristics of chalcone prototypes against trypomastigotes of T. cruzi.

Keywords

Chalcone; Drug discovery; Multivariate analysis; Trypanocidal activity; Trypanosoma cruzi.

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