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

Autor:	Luciano Vasconcellos Pacheco, Tatiana Barbosa dos Santos Magalhães, Lourenço Luis Botelho de Santana, Saul Vislei Simões da Silva, Milena Botelho Pereira Soares, Cleonice Creusa dos Santos, Silvia Lima Costa, Jéssica Teles Souza, Elisalva Teixeira Guimarães, Érica N. Soares, Orlando Maia Barboza, Aníbal de Freitas Santos Júnior, Victor Diogenes Amaral da Silva, Cássio Santana Meira, Ivanilson Pimenta Santos
Rok vydání:	2021
Předmět:	Antioxidant antioxidant synthesis medicine.medical_treatment antileishmania Anti-Inflammatory Agents Antiprotozoal Agents quercetin pentaacetate Pharmaceutical Science Organic chemistry Antineoplastic Agents HL-60 Cells Pharmacology Antioxidants Article Analytical Chemistry quercetin chemistry.chemical_compound Mice QD241-441 Drug Discovery medicine Animals Humans Physical and Theoretical Chemistry Cytotoxicity IC50 anti-inflammatory Mice Inbred BALB C Chemistry Acetylation Hep G2 Cells Cytokine Chemistry (miscellaneous) Cell culture Cancer cell Molecular Medicine Tumor necrosis factor alpha Quercetin cytotoxicity activity
Zdroj:	Molecules Molecules, Vol 26, Iss 6923, p 6923 (2021) Volume 26 Issue 22
ISSN:	1420-3049
Popis:	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 < 0.05) Q and Q5 showed higher activity at concentrations > 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39ca88e22af84f117d5689e11cd7548f https://pubmed.ncbi.nlm.nih.gov/34834016 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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