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

Author(s)

Rodrigues, Debora Munhoz ^[1] ; Portapilla, Gisele Bulhoes ^[1] ; Silva, Guilherme Martins ^[2] ; Duarte, Andressa ^[3] ; Rotta, Cristiana Goncalez ^[1] ; da Silva, Carlos Henrique Tomich de Paula ^{[1, 2]} ; de Albuquerque, Sergio ^[1] ; Bastos, Jairo Kenupp ^[1] ; Campo, Vanessa Leiria ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Av Cafe S-N, BR-14040930 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Preto, Av Cafe S-N, BR-14040901 Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Dept Pathol & Forens Med, Sch Med, Av Cafe S-N, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Barao Maua Univ Ctr, St Ramos Azevedo 423, BR-14090180 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry; v. 47, OCT 1 2021.
• Web of Science Citations: 0

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 PNT2) to evaluate their cytotoxicity. In general, the best activity was observed for compound 6e, derived from drupanin, which exhibited half-maximal inhibitory concentration (IC50) of 9.6 +/- 3 mu M and selectivity index (SI) of 5.5 against MCF-7 cells. In silico studies 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. (AU)

• FAPESP's process: 17/04138-8 - Attainment of chemical, analytical, biological, pharmacological and technological studies to fill the gaps on the development of Brazilian propolis sector
• Grantee: Jairo Kenupp Bastos
• Support Opportunities: Research Projects - Thematic Grants