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

Autor: Gomes KS; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP 09210-580, Brazil., da Costa-Silva TA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP 09210-580, Brazil., Oliveira IH; Departamento de Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972-270, Brazil., Aguilar AM; Departamento de Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972-270, Brazil., Oliveira-Silva D; Departamento de Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972-270, Brazil., Uemi M; Departamento de Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972-270, Brazil., Silva WA; Instituto de Química, Universidade de Brasília, Brasília, DF 70910-900, Brazil., Melo LR; Instituto de Química, Universidade de Brasília, Brasília, DF 70910-900, Brazil., Andrade CKZ; Instituto de Química, Universidade de Brasília, Brasília, DF 70910-900, Brazil., Tempone AG; Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, São Paulo, SP 01246-000, Brazil., Baldim JL; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP 09210-580, Brazil. Electronic address: jotaelebaldim@gmail.com., Lago JHG; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP 09210-580, Brazil. Electronic address: joao.lago@ufabc.edu.br.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Jun 15; Vol. 29 (12), pp. 1459-1462. Date of Electronic Publication: 2019 Apr 12.
DOI: 10.1016/j.bmcl.2019.04.020
Abstrakt: 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.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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