{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:40:00Z","timestamp":1792456800235,"version":"4.5.0"},"reference-count":55,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u2022+. 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 &lt; 0.05); Q and Q5 showed higher activity at concentrations &gt; 40\u00b5M when compared to dexamethasone (20 \u00b5M). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC50 &gt; 80 \u00b5M). Finally, the cytotoxic superiority of Q5 was verified (IC50 = 11 \u00b5M), which, at 50 \u00b5M 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.<\/jats:p>","DOI":"10.3390\/molecules26226923","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T09:16:11Z","timestamp":1637140571000},"page":"6923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Structural Design, Synthesis and Antioxidant, Antileishmania, Anti-Inflammatory and Anticancer Activities of a Novel Quercetin Acetylated Derivative"],"prefix":"10.3390","volume":"26","author":[{"given":"Saul Vislei Sim\u00f5es","family":"da Silva","sequence":"first","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando Maia","family":"Barboza","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica Teles","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Federal University of Bahia, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9rica Novaes","family":"Soares","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Federal University of Bahia, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleonice Creusa","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Federal University of Bahia, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano Vasconcellos","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"},{"name":"Gon\u00e7alo Moniz Institute, FIOCRUZ, Salvador 40296-710, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivanilson Pimenta","family":"Santos","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, FIOCRUZ, Salvador 40296-710, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana Barbosa dos Santos","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena Botelho Pereira","family":"Soares","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, FIOCRUZ, Salvador 40296-710, BA, Brazil"},{"name":"SENAI Institute of Innovation in Health Advanced Systems (CIMATEC ISI SAS), University Center SENAI\/CIMATEC, Salvador 41650-010, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisalva Teixeira","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"},{"name":"Gon\u00e7alo Moniz Institute, FIOCRUZ, Salvador 40296-710, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1ssio Santana","family":"Meira","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"},{"name":"Gon\u00e7alo Moniz Institute, FIOCRUZ, Salvador 40296-710, BA, Brazil"},{"name":"SENAI Institute of Innovation in Health Advanced Systems (CIMATEC ISI SAS), University Center SENAI\/CIMATEC, Salvador 41650-010, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8975-3871","authenticated-orcid":false,"given":"Silvia Lima","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Federal University of Bahia, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Di\u00f3genes Amaral","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Federal University of Bahia, Salvador 40231-300, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louren\u00e7o Lu\u00eds Botelho","family":"de Santana","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3022-0771","authenticated-orcid":false,"given":"An\u00edbal","family":"de Freitas Santos J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/0278-6915(95)00077-1","article-title":"Review of the biology of quercetin and related bioflavonoids","volume":"33","author":"Formica","year":"1995","journal-title":"Food Chem. Toxicol."},{"key":"ref_2","first-page":"407","article-title":"Quercetin and its derivatives: Chemical structure and bioactivity\u2014A review","volume":"58","author":"Materska","year":"2008","journal-title":"Pol. J. Food Nutr. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ajps.2017.08.004","article-title":"Bioactive flavonoids in medicinal plants: Structure, activity and biological fate","volume":"13","author":"Wang","year":"2018","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.fitote.2015.09.018","article-title":"Quercetin: A flavonol with multifaceted therapeutic applications?","volume":"106","year":"2015","journal-title":"Fitoterapia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5232","DOI":"10.1039\/C9AN00948E","article-title":"Flavonoids induce cell death in: Leishmania amazonensis: In vitro characterization by flow cytometry and Raman spectroscopy","volume":"144","author":"Queiroz","year":"2019","journal-title":"Analyst"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2478\/helm-2021-0004","article-title":"Antiparasitic effects of selected isoflavones on flatworms","volume":"58","year":"2021","journal-title":"Helminthologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/j.foodchem.2013.05.025","article-title":"Dietary flavonoids fisetin, luteolin and their derived compounds inhibit arginase, a central enzyme in Leishmania (Leishmania) amazonensis infection","volume":"141","author":"Manjolin","year":"2013","journal-title":"Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1128\/AAC.50.4.1352-1364.2006","article-title":"Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: In vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies","volume":"50","author":"Tasdemir","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s00204-014-1300-0","article-title":"Quercetin induces mitochondrial-derived apoptosis via reactive oxygen species-mediated ERK activation in HL-60 leukemia cells and xenograft","volume":"89","author":"Lee","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/ptr.4753","article-title":"Inhibition of proinflammatory biomarkers in THP1 macrophages by polyphenols derived from chamomile, meadowsweet and willow bark","volume":"27","author":"Drummond","year":"2013","journal-title":"Phytother Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s00415-016-8355-1","article-title":"Outcome in unresectable glioblastoma: MGMT promoter methylation makes the difference","volume":"264","author":"Thon","year":"2016","journal-title":"J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/S0959-8049(00)00430-5","article-title":"Effects of a novel synthetic retinoid on malignant glioma in vitro inhibition of cell proliferation, induction of apoptosis and differentiation","volume":"37","author":"Perzelova","year":"2001","journal-title":"Eur. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"856349","DOI":"10.1155\/2015\/856349","article-title":"Effect and mechanism of total flavonoids extracted from Cotinus coggygria against Glioblastoma cancer in vitro and in vivo","volume":"2015","author":"Wang","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cbi.2015.07.014","article-title":"Flavonoids suppress human glioblastoma cell growth by inhibiting cell metabolism, migration, and by regulating extracellular matrix proteins and metalloproteinases expression","volume":"242","author":"Santos","year":"2015","journal-title":"Chem.-Biol. Interact."},{"key":"ref_15","first-page":"16","article-title":"Low concentrations of flavonoid-rich fraction of shallot extract induce delayed-type hypersensitivity and TH1 cytokine IFN\u03b3 expression in BALB\/c mice","volume":"3","author":"Farhadi","year":"2014","journal-title":"Int. J. Mol. Cell. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0167-4889(02)00328-2","article-title":"The flavonoid, quercetin, differentially regulates Th-1 (IFN\u03b3) and Th-2 (IL4) cytokine gene expression by normal peripheral blood mononuclear cells","volume":"1593","author":"Nair","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Massi, A., Bortolini, O., Ragno, D., Bernardi, T., Sacchetti, G., Tacchini, M., and De Risi, C. (2017). Research progress in the modification of quercetin leading to anticancer agents. Molecules, 22.","DOI":"10.3390\/molecules22081270"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.tetlet.2014.01.081","article-title":"Unveiling the chemistry behind bromination of quercetin: The \u201cviolet chromogen\u201d","volume":"55","author":"Foti","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.bmcl.2014.11.039","article-title":"The synthesis, antimalarial activity and CoMFA analysis of novel aminoalkylated quercetin analogs","volume":"25","author":"Helgren","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.cbi.2014.01.017","article-title":"Novel oxime based flavanone, naringin-oxime: Synthesis, characterization and screening for antioxidant activity","volume":"212","author":"Bener","year":"2014","journal-title":"Chem.-Biol. Interact."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.3390\/molecules15074722","article-title":"Regioselective O-derivatization of quercetin via ester intermediates. An improved synthesis of rhamnetin and development of a new mitochondriotropic derivative","volume":"15","author":"Mattarei","year":"2010","journal-title":"Molecules"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2478\/intox-2013-0031","article-title":"Antioxidant action and cytotoxicity on HeLa and NIH-3T3 cells of new quercetin derivatives","volume":"6","author":"Veverka","year":"2013","journal-title":"Interdiscip. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1021\/jm060912x","article-title":"Ester-based precursors to increase the bioavailability of quercetin","volume":"50","author":"Biasutto","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"64","DOI":"10.4103\/abr.abr_76_17","article-title":"Synthesis and in vitro leishmanicidal activities of six quercetin derivatives","volume":"7","author":"Mohajeri","year":"2018","journal-title":"Adv. Biomed. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.foodchem.2011.08.074","article-title":"Tin(II)-quercetin complex: Synthesis, spectral characterisation and antioxidant activity","volume":"131","author":"Dehghan","year":"2012","journal-title":"Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"130394","DOI":"10.1016\/j.foodchem.2021.130394","article-title":"Quercetin and its ester derivatives inhibit oxidation of food, LDL and DNA","volume":"364","author":"Oh","year":"2021","journal-title":"Food Chem."},{"key":"ref_27","first-page":"e14666","article-title":"Reactive oxygen species production and mitochondrial dysfunction contribute to quercetin induced death in Leishmania amazonensis","volume":"8","author":"Inacio","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108745","DOI":"10.1016\/j.biopha.2019.108745","article-title":"Quercetin promotes antipromastigote effect by increasing the ROS production and anti-amastigote by upregulating Nrf2\/HO-1 expression, affecting iron availability","volume":"113","author":"Cataneo","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1093\/jac\/dkn053","article-title":"Quercetin interferes with iron metabolism in Leishmania donovani and targets ribonucleotide reductase to exert leishmanicidal activity","volume":"61","author":"Sen","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/BF03401792","article-title":"Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis","volume":"6","author":"Mittra","year":"2000","journal-title":"Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.biopha.2016.10.011","article-title":"Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions","volume":"84","author":"Suganthy","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12640-016-9600-1","article-title":"Impact of plant-derived flavonoids on neurodegenerative diseases","volume":"30","author":"Costa","year":"2016","journal-title":"Neurotox. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M.T., Wang, S., Liu, H., and Yin, Y. (2016). Quercetin, inflammation and immunity. Nutrients, 8.","DOI":"10.3390\/nu8030167"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fimmu.2019.00051","article-title":"Immunomodulatory effects of flavonoids: Possible induction of T CD4+ regulatory cells through suppression of mTOR pathway signaling activity","volume":"10","author":"Hosseinzade","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/jcb.1184","article-title":"Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages","volume":"82","author":"Chen","year":"2001","journal-title":"J. Cell Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1271\/bbb.90253","article-title":"Clarification of the role of quercetin hydroxyl groups in superoxide generation and cell apoptosis by chemical modification","volume":"73","author":"Sakao","year":"2009","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cbi.2017.07.004","article-title":"The flavonoid rutin modulates microglial\/macrophage activation to a CD150\/CD206 M2 phenotype","volume":"274","author":"Silva","year":"2017","journal-title":"Chem.-Biol. Interact."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s13765-015-0050-x","article-title":"Synthesis of alkyl quercetin derivatives","volume":"58","author":"Kim","year":"2015","journal-title":"J. Korean Soc. Appl. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bao, D., Wang, J., Pang, X., and Liu, H. (2017). Protective effect of quercetin against oxidative stress-induced cytotoxicity in rat pheochromocytoma (PC-12) Cells. Molecules, 22.","DOI":"10.3390\/molecules22071122"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.bbi.2019.05.003","article-title":"The flavonoid rutin and its aglycone quercetin modulate the micr\u00f3glia inflammatory profile improving antiglioma activity","volume":"85","author":"Coelho","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1111\/j.1349-7006.2009.01215.x","article-title":"Resveratrol and quercetin cooperate to induce senescence-like growth arrest in C6 rat glioma cells","volume":"100","author":"Zamin","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.fct.2017.02.010","article-title":"Quercetin exerts preventive, ameliorative and prophylactic effects on cadmium chloride\u2013induced oxidative stress in the uterus and ovaries of female Wistar rats","volume":"102","author":"Nna","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1007\/s13277-015-4125-4","article-title":"Inhibition of autophagy induced by quercetin at a late stage enhances cytotoxic effects on glioma cells","volume":"37","author":"Bi","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ejps.2017.01.036","article-title":"Quercetin derivatives as potent inducers of selective cytotoxicity in glioma cells","volume":"101","author":"Grasso","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.tox.2006.03.007","article-title":"Quercetin inhibition of ROS-dependent and -independent apoptosis in rat glioma C6 cells","volume":"223","author":"Chen","year":"2006","journal-title":"Toxicology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bjp.2015.05.013","article-title":"Flavonoids from the Brazilian plant croton betulaster inhibit the growth of human glioblastoma cells and induce apoptosis","volume":"26","author":"Coelho","year":"2016","journal-title":"Braz. J. Pharmacog."},{"key":"ref_47","first-page":"1","article-title":"Antiglioma potential of flavonoids","volume":"6","author":"Costa","year":"2014","journal-title":"J. Bioanal. Biomed."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.foodchem.2003.12.039","article-title":"Fe(III) reductive and free radical-scavenging properties of summer savory (Satureja hortensis L.) extract and subfractions","volume":"88","author":"Dorman","year":"2004","journal-title":"Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e170345","DOI":"10.1590\/0074-02760170345","article-title":"In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195","volume":"113","author":"Guedes","year":"2018","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1126\/science.161.3839.370","article-title":"Differentiated rat glial cell strain in tissue culture","volume":"161","author":"Benda","year":"1968","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neuint.2016.06.004","article-title":"The classical photoactivated drug 8-methoxypsoralen and related compounds are effective without UV light irradiation against glioma cells","volume":"99","author":"Oliveira","year":"2016","journal-title":"Neurochem. Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0022-1759(94)90396-4","article-title":"A new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes an alternative to [3H] thymidine incorporation assay","volume":"170","author":"Ahmed","year":"1994","journal-title":"J. Immunol. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0022-1759(89)90397-9","article-title":"Re-examination, and further development of a precise and rapid dye method for measuring cell growth\/cell kill","volume":"119","author":"Hansen","year":"1989","journal-title":"J. Immunol. Methods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"130479","DOI":"10.1016\/j.foodchem.2021.130479","article-title":"Identification of bioactive metabolites from corn silk extracts by a combination of metabolite profiling, univariate statistical analysis and chemometrics","volume":"365","author":"Hora","year":"2021","journal-title":"Food Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0003-2697(82)90118-X","article-title":"Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids","volume":"126","author":"Green","year":"1982","journal-title":"Anal. Biochem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/22\/6923\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:31:27Z","timestamp":1760167887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/22\/6923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":55,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["molecules26226923"],"URL":"https:\/\/doi.org\/10.3390\/molecules26226923","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,17]]}}}