Molecules (Nov 2021)

Structural Design, Synthesis and Antioxidant, Antileishmania, Anti-Inflammatory and Anticancer Activities of a Novel Quercetin Acetylated Derivative

  • Saul Vislei Simões da Silva,
  • Orlando Maia Barboza,
  • Jéssica Teles Souza,
  • Érica Novaes Soares,
  • Cleonice Creusa dos Santos,
  • Luciano Vasconcellos Pacheco,
  • Ivanilson Pimenta Santos,
  • Tatiana Barbosa dos Santos Magalhães,
  • Milena Botelho Pereira Soares,
  • Elisalva Teixeira Guimarães,
  • Cássio Santana Meira,
  • Silvia Lima Costa,
  • Victor Diógenes Amaral da Silva,
  • Lourenço Luís Botelho de Santana,
  • Aníbal de Freitas Santos Júnior

DOI
https://doi.org/10.3390/molecules26226923
Journal volume & issue
Vol. 26, no. 22
p. 6923

Abstract

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Quercetin (Q) is a bioflavonoid with biological potential; however, poor solubility in water, extensive enzymatic metabolism and a reduced bioavailability limit its biopharmacological use. The aim of this study was to perform structural modification in Q by acetylation, thus, obtaining the quercetin pentaacetate (Q5) analogue, in order to investigate the biological potentials (antioxidant, antileishmania, anti-inflammatory and cytotoxicity activities) in cell cultures. Q5 was characterized by FTIR, 1H and 13C NMR spectra. The antioxidant potential was evaluated against the radical ABTS•+. The anti-inflammatory potential was evaluated by measuring the pro-inflammatory cytokine tumor necrosis factor (TNF) and the production of nitric oxide (NO) in peritoneal macrophages from BALB/c mice. Cytotoxicity tests were performed using the AlamarBlue method in cancer cells HepG2 (human hepatocarcinoma), HL-60 (promyelocytic leukemia) and MCR-5 (healthy human lung fibroblasts) as well as the MTT method for C6 cell cultures (rat glioma). Q and Q5 showed antioxidant activity of 29% and 18%, respectively, which is justified by the replacement of hydroxyls by acetyl groups. Q and Q5 showed concentration-dependent reductions in NO and TNF production (p 40µM when compared to dexamethasone (20 µM). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC50 > 80 µM). Finally, the cytotoxic superiority of Q5 was verified (IC50 = 11 µM), which, at 50 µM for 24 h, induced changes in the morphology of C6 glioma cells characterized by a round body shape (not yet reported in the literature). The analogue Q5 had potential biological effects and may be promising for further investigations against other cell cultures, particularly neural ones.

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