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

Autor(es):Mostrar menos -

Gomes, Kaio S. ^[1] ; da Costa-Silva, Thais A. ^[1] ; Oliveira, Igor H. ^[2] ; Aguilar, Andrea M. ^[2] ; Oliveira-Silva, Diogo ^[2] ; Uemi, Miriam ^[2] ; Silva, Wender A. ^[3] ; Melo, Lennine R. ^[3] ; Andrade, Carlos Kleber Z. ^[3] ; Tempone, Andre G. ^[4] ; Baldim, Joao L. ^[1] ; Lago, Joao Henrique G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

^[2] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Quim, BR-09972270 Diadema, SP - Brazil

^[3] Univ Brasilia, Inst Quim, BR-70910900 Brasilia, DF - Brazil

^[4] Adolfo Lutz Inst, Ctr Parasitol & Micol, BR-01246000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry Letters; v. 29, n. 12, p. 1459-1462, JUN 15 2019.
• Citações Web of Science: 0

Resumo

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, alpha,beta-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. (AU)

• Processo FAPESP: 18/10279-6 - Seleção e Otimização de Novos Candidatos a Fármacos para Leishmaniose e Doença de Chagas
• Beneficiário: André Gustavo Tempone Cardoso
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07885-1 - Biomoléculas oriundas de espécies vegetais de áreas remanescentes da Mata Atlântica e do Cerrado para tratamento de doenças tropicais negligenciadas - aspectos químicos e farmacológicos
• Beneficiário: João Henrique Ghilardi Lago
• Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Regular