2. Academic Validation
  3. Synthesis, antitumor activity and in silico analyses of amino acid derivatives of artepillin C, drupanin and baccharin from green propolis

Synthesis, antitumor activity and in silico analyses of amino acid derivatives of artepillin C, drupanin and baccharin from green propolis

  • Bioorg Med Chem. 2021 Oct 1;47:116372. doi: 10.1016/j.bmc.2021.116372.
Débora Munhoz Rodrigues 1,  Gisele Bulhões Portapilla 1,  Guilherme Martins Silva 2,  Andressa Duarte 3,  Cristiana Gonçalez Rotta 1,  Carlos Henrique Tomich de Paula da Silva 4,  Sérgio de Albuquerque 1,  Jairo Kenupp Bastos 1,  Vanessa Leiria Campo 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences of Ribeirão Preto - University of São Paulo, Av. do Café S/N, 14040-930 Ribeirão Preto, SP, Brazil.
  • 2 Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - University of São Paulo, Av. do Café S/N, 14040-901 Ribeirão Preto, SP, Brazil.
  • 3 Department of Pathology and Forensic Medicine - University of São Paulo, Av. do Café S/N, 14049-900 Ribeirão Preto Medical School, SP, Brazil.
  • 4 School of Pharmaceutical Sciences of Ribeirão Preto - University of São Paulo, Av. do Café S/N, 14040-930 Ribeirão Preto, SP, Brazil; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - University of São Paulo, Av. do Café S/N, 14040-901 Ribeirão Preto, SP, Brazil.
  • 5 School of Pharmaceutical Sciences of Ribeirão Preto - University of São Paulo, Av. do Café S/N, 14040-930 Ribeirão Preto, SP, Brazil; Barão de Mauá University Center, St. Ramos de Azevedo 423, 14090-180 Ribeirão Preto, SP, Brazil. Electronic address: [email protected].
PMID: 34454129 DOI: 10.1016/j.bmc.2021.116372
Abstract

Breast Cancer has the highest incidence and mortality in females, while prostate Cancer has the second-highest incidence in males. Studies have shown that compounds from Brazilian green propolis have antitumor activities and can selectively inhibit the AKR1C3 Enzyme, overexpressed in hormone-dependent prostate and breast tumors. Thus, in an attempt to develop new cytotoxic inhibitors against these cancers, three prenylated compounds, artepillin C, drupanin and baccharin, were isolated from green propolis to synthesize new derivatives via coupling reactions with different Amino acids. All obtained derivatives were submitted to antiproliferative assays against four Cancer cells (MCF-7, MDA MB-231, PC-3, and DU145) and two normal cell lines (MCF-10A and PNT-2) to evaluate their cytotoxicity. In general, the best activity was observed for compound6e, derived from drupanin, which exhibited half-maximal inhibitory concentration (IC50) of 9.6 ± 3 μM and selectivity index (SI) of 5.5 against MCF-7 cells.In silicostudies demonstrated that these derivatives present coherent docking interactions and binding modes against AKR1C3, which might represent a possible mechanism of inhibition in MCF-7 cells.

Keywords

AKR1C3 docking; Baccharis dracunculifolia; Breast and prostate cancer; Natural products; Semisynthesis.

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