Abstract：Quercetin is a flavonoid compound, which is widely present in various vegetables, fruits and Chinese herbal medicines that people eat daily. Quercetin is a natural antioxidant and has a wide range of pharmacological activities. It can regulate the intracellular and extracellular signaling pathways related to the progression of many diseases, possessing anti-inflammatory, anti-viral, anti-cancer activities, thus can be used to prevent and treat cardiovascular and cerebrovascular diseases. Its structural characteristics and low bioavailability has limited its clinical application. Quercetin has been modified into derivatives through structural optimization with excellent performance, good solubility, high bioavailability, stable metabolism, low toxic and side effects, and significant biological activity. This article reviews the quercetin derivatives synthesized using quercetin as the lead compound in the past decade, and highlights the pharmacological effects of these derivatives, such as anti-inflammatory, effect hypoglycemic, anti-cancer, anti-Alzheimer's disease, anti-malaria, etc., to lay the foundation for the development and utilization of natural compounds.
李阳杰, 姜亚玲, 刘秋伟, 翟广玉. 槲皮素衍生物的生物活性研究进展[J]. 中国药学杂志, 2021, 56(3): 175-180.
LI Yang-jie, JIANG Ya-ling, LIU Qiu-wei, ZHAI Guang-yu. Progress in Research on Biological Activity of Quercetin Derivatives. Chinese Pharmaceutical Journal, 2021, 56(3): 175-180.
XU D, HU M J, WANG Y Q, et al. Antioxidant activities of quercetin and its complexes for medicinal application[J]. Molecules, 2019, 24(6):1123-1140.
[2]
TAN B L, NORHAIZAN M E, LIEW W P, et al. Antioxidant and oxidative stress: a mutual interplay in age-related diseases[J]. Front Pharmacol, 2018, 9: 1162.
[3]
FUENTES J, ATALA E,PASTENE E, et al. Quercetin oxidation paradoxically enhances its antioxidant and cytoprotective properties[J]. J Agric Food Chem, 2017, 65(50): 11002-11010.
[4]
SOKOLOVÁ R, RAMEŠOVÁ Š, DEGANO I, et al. The oxidation of natural flavonoid quercetin[J]. Chem Commun, 2012, 48(28): 3433-3435.
[5]
PINGILI R B, CHALLA S R, PAWAR A K, et al. A systematic review on hepatoprotective activity of quercetin against various drugs and toxic agents: evidence from preclinical studies[J]. Phytother Res, 2020, 34:5-32.
[6]
KASIRI N, RAHMATI M, AHMADI L, et al. Therapeutic potential of quercetin on human breast cancer in different dimensions[J]. Inflammopharmacology, 2020, 28(1): 39-62.
[7]
ANAND D A V, ARULMOLI R, PARASURAMAN S. Overviews of biological importance of quercetin: a bioactive flavonoid[J]. Phcog Rev, 2016, 10(20):84-89.
[8]
JAKARIA M, AZAM S, JO S H, et al. Potential therapeutic targets of quercetin and its derivatives: its role in the therapy of cognitive impairment[J]. J Clin Med, 2019, 8(11):1789.
[9]
CHEN C, ZHOU J, JI C Y. Quercetin: a potential drug to reverse multidrug resistance[J]. Life Sci, 2010, 87(11-12):333-338.
[10]
SELVARAJ M, MICHAŁ T, KRYSTYNA S W, et al. Hepatoprotective effect of quercetin: from chemistry to medicine[J]. Food Chem Toxicol, 2017,108:365-374.
[11]
ASMA V,ZAHRA S,AHMAD M, et al. Quercetin and cancer: new insights into its therapeutic efects on ovarian cancer cells[J]. Cell Biosci, 2020, 10:32.
[12]
CIONE E, TORRE L T, CANNATARO C, et al. Quercetin, epigallocatechin gallate, curcumin, and resveratrol: from dietary sources to human microRNA modulation[J]. Molecules, 2020, 25(1): 63.
[13]
KIM D H, HAROON K, HAMMAD U, et al. MicroRNA targeting by quercetin in cancer treatment and chemoprotection[J]. Pharmacol Res, 2019, 147:104346.
[14]
JONES R S, PARKER M D, MORRIS M E. Quercetin, morin, luteolin, and phloretin are dietary flavonoid inhibitors of monocarboxylate transporter 6[J]. Mol Pharm, 2017, 14(9):2930-2936.
[15]
TANG S M, DENG X T, ZHOU J, et al. Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects[J]. Biomed Pharmacother,2020, 121:109604.
[16]
NATARAJAN T D, RAMASAMY J R, PALANISAMY K, et al. Nutraceutical potentials of synergic foods: a systematic review[J]. J Ethnic Foods, 2019, 6(1): 1-7.
[17]
GUPTA A, BIRHMAN K, RAHEJA I, et al. Quercetin: a wonder bioflavonoid with therapeutic potential in disease management[J]. Asian Pac J Trop Med, 2016, 6(3):248-252.
[18]
D'ANDREA G. Quercetin: a flflavonol with multifaceted therapeutic applications? [J]. Fitoterapia, 2015, 106: 256-271.
[19]
QU W T, ZHU W, ZHAI G Y, et al. Research progress of synthesis and biological activity of quercetin derivatives[J]. Chem Res(化学研究), 2012, 23(4):84,101-110.
[20]
JIA J J, GUO Z Y, LIANG Y H, et al. Synthesis and anti-tumor activities of quercetin and its derivatives[J]. Chin Pharm J(中国药学杂志), 2016, 51(23):2013-2017.
[21]
BULE M, ABDURAHMAN A, NIKFAR S, et al. Antidiabetic effect of quercetin: a systematic review and Meta-analysis of animal studies[J]. Food Chem Toxicol, 2019, 125:494-502.
[22]
MASSI A, BORTOLINI O, RAGNO D, et al. Research progress in the modifification of quercetin leading to anticancer agents[J]. Molecules, 2017, 22(8): 1270.
[23]
SHARMA A, KASHYAP D, SAK K, et al. Therapeutic charm of quercetin and its derivatives: a review of research and patents[J]. Pharm Pat Anal, 2018,7(1):15-32.
[24]
NOBELOS P T, TZIONA P, POPTSIS A, et al. Novel polyfunctional esters of ibuprofen and ketoprofenwith hypolipidemic, lipoxygenase inhibitory and enhancedanti-inflammatory activity Panagiotis[J]. Med Chem Res, 2017,26:461-472.
[25]
RASHEED A, LATHIKA G, RAJU Y P, et al. Synthesis and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and L-tryptophanas gastrosparing NSAIDS[J]. Med Chem Res, 2016, 25:70-82.
[26]
SEO J Y, PANDEY R P, LEE J, et al. Quercetin 3-O-xyloside ameliorates acute pancreatitis in vitro via thereduction of ER stress and enhancement of apoptosis[J]. Phytomedicine, 2019, 55: 40-49.
[27]
YONG H M, BAI R Y, BI F Y, et al. Synthesis, characterization, antioxidant and antimicrobial activities of starch aldehyde-quercetin conjugate[J]. Int J Biol Macromol, 2020, 156:462-470.
[28]
SUMUDU W, ZIAULLAH, RUPASINGHE H. Long chain fatty acid esters of quercetin-3-O-glucoside attenuate H2O2-induced acute cytotoxicity in human lung fibroblasts and primary hepatocytes[J]. Molecules, 2016, 21(4):452.
[29]
BURAVLEV E V, SHEVCHENKO O G, CHUKICHEVA I Y, et al. Synthesis and membrane-protective properties of aminomethyl derivatives of quercetin at the C-8 position[J]. Chem Pap, 2018, 72(1): 201-208.
[30]
GUIMARES G C, PIVA H R M, ARANU'JO G C, et al. Binding investigation between M2-1 protein from hRSV and acetylated quercetin derivatives:1H-NMR, fluorescence spectroscopy, andmolecular docking[J]. Int J Biol Macromol, 2018, 111: 33-38.
[31]
NETTORE I C, ROCCA C, MANCINO G, et al. Quercetin and its derivative Q2 modulate chromatin dynamics in adipogenesis and Q2 prevents obesity and metabolic disorders in rats[J]. J Nutr Biochem, 2019, 69: 151-162.
[32]
CARULLO G, PERRI M, MANETTI F, et al. Quercetin-3-oleoyl derivatives as new GPR40 agonists: molecular docking studies and functional evaluation Gabriele[J]. Bioorg Med Chem Lett,2019, 29(14):1761-1764.
[33]
ZHU J Z, ZHANG B, TAN C P, et al. α-Glucosidase inhibitors: consistency of in silico docking data with in vitro inhibitory data and inhibitory effect prediction of quercetin derivatives[J]. Food Funct, 2019, 10: 6312-6321.
[34]
NICOLA S, MATTAREI A, ESPINA V, et al. Potential anti-cancer activity of 7-O-pentyl quercetin: efficient,membrane-targeted kinase inhibition and pro-oxidant effect[J]. Parmacol Res, 2017, 124: 9-19.
[35]
AYAN M, MISHASIS S, KOTLA N, et al. Semisynthetic quercetin derivatives with potent antitumor activityin colon carcinoma[J]. ACS Omega, 2019, 4: 7285-7298.
[36]
KOSEI Y, SYEDA H, TOHRU M, et al. 3,4,7-O-trimethyl quercetin inhibits invasion and migration of ovarian cancer cells[J]. Anticancer Res, 2017, 37 (6): 2823-2829.
[37]
KELLICI T F, CHATZIATHANASIADOU M V, LEE M S, et al. Rational design and structure-activity relationship studies of quercetin-amino acid hybrids targeting the anti-apoptotic protein Bcl-xL[J]. Org Biomol Chem, 2017, 15(37):7956-7976.
[38]
ALANSSARI R A, ELIAS R S, ALJADAAN S A, et al. Synthesis, Ant proliferative activity and docking study of new quercetin derivatives against MDA-MB231 breast cancer cell lines[J]. Am J Appl Sci, 2019, 16 (5): 143-161.
[39]
GENÇKAL H M, ERKISA M, ALPER P, et al. Mixed ligand complexes of Co(Ⅱ), Ni(Ⅱ) and Cu(Ⅱ) with quercetin and diimine ligands: synthesis, characterization, anti-cancer and anti-oxidant activity[J]. J Biol Inorg Chem, 2020, 25(1):161-177.
[40]
DASILVA W M B, DEOLIVEIRA P S, ALVES D R, et al. Synthesis of quercetin-metal complexes, in vitro and in silico anticholinesterase and antioxidant evaluation, and in vivo toxicological and anxiolitic activities[J]. Neurotox Res, 2020, 37:893-903.
[41]
ROUANE A, TCHOUAR N, KERASSA A, et al. Structure-based virtual screening and drug-like of quercetin derivatives with anti-malaria activity[J]. Rev Ther Sci, 2017, 5:1-11.
[42]
MAGAR R T, SOHNG J K. A review on structure, modifications and structure-activity relation of quercetin and its derivatives[J]. J Microbiol Biotechnol, 2020, 30(1): 11-20.
2021, Vol. 56 
