Abstract：OBJECTIVE To synthesize quercetin-3-O-acyl ester and explore the antitumor activity.METHODS Using cheap rutin as the raw material, twelve kinds of quercetin-3-O-acyl esters were obtained by benzylation protection, acid hydrolysis, esterification reaction, and then catalytic hydrogenation and debenzylation by Pd/C. Then, infrared(IR), hydrogen spectrum(1H-NMR), carbon spectrum(13C-NMR), and liquid chromatography-mass spectrometry(ESI-MS) were used to determine the structure. Meanwhile, the antioxidant activities of the twelve target compounds were investigated by o-phenanthroline method and 1,1-diphenyl-2-picrylhydrazyl( DPPH ) method, and the antitumor activities were determined by 3-(4,5-dimethylthiazol-2) -2,5 - diphenyltetrazolium bromide(MTT) method.RESULTS The structure of the target compounds was determined by spectroscopic analysis, and the results of antioxidant activity showed that the SC50 of the most target compounds was less than or equal to quercetin, which suggested that 3-OH is not an essential group for the antioxidant activity of quercetin, and the proliferation inhibition of the target compounds on human esophageal cancer cell EC109, human esophageal squamous cell carcinoma EC9706, human gastric cancer cell MGC-803 and human prostate cancer cell PC-3 in vitro was enhanced.CONCLUSION Twelve target compounds are synthesized and their inhibitory effects on tumor cell proliferation are significantly enhanced compared with quercetin.
SALEHI B, MACHIN L, MONZOTE L, et al. Therapeutic potential of quercetin: new insights and perspectives for human health[J]. ACS Omega,2020,5(20): 11849-11872.
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. Doi:10.3390/molecules25010063.
JOCELYN F, ELÍAS A, EDGAR P, et al. Quercetin oxidation paradoxically enhances its antioxidant and cytoprotective properties[J]. J Agric Food Chem,2017,65(50):11002-11010.
LESJAK M, BEARA I, SIMIN I, et al. Antioxidant and anti-inflammatory activities of quercetin and its derivatives[J]. J Funct Foods,2018,40: 68-75. Doi: 10.1016/j.jff.2017.10.047.
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. Doi:10.1016/j.biopha.2019.109604.
ABDUR R, IMRAN M, IMTIAZ A K, et al. Anticancer potential of quercetin: A comprehensive review[J].Phytother Res,2018,32(11):2109-2130.
DHARAMBIR K, SONAM M, KATRIN S, et al. Molecular mechanisms of action of quercetin in cancer: recent advances[J].Tumor Biol,2016,37(10):12927-12939.
REYES F M,CARRASCO P C. The anti-cancer effect of quercetin: molecular implications in cancer metabolism[J]. Int J Mol Sci,2019,20(13):3177. Doi: 10.3390/ijms20133177.
RAHUL V P, BHUPENDRA M M, SURENDRA K S, et al. Therapeutic potential of quercetin as a cardiovascular agent[J]. Eur J Med Chem,2018,155:889-904. Doi:10.1016/j.ejmech.2018.06.053.
NATARAJAN T D, RAMASAMY J R, PALANISAMY K,et al. Nutraceutical potentials of synergic foods: a systematic review[J]. J Ethn Food,2019,6(1): 1-7.
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.
D′ANDREA G. Quercetin: A flflavonol with multifaceted therapeutic applications?[J]. Fitoterapia, 2015, 106:256-271. Doi:10.1016/j.fitote.2015.09.018.
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. Doi:0278-6915(2019)125:<494:502;RAMOAS>2.0.TX;2-5.
MASSI A, BORTOLINI O, RAGNO D, et al. Research progress in the modification ofquercetin leading to anticancer agents[J]. Molecules,2017,22(8):1270. Doi: 10.3390/molecules22081270.
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.
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.
PETRONELA Z,MILAN S,LUCIA R,et al. Novel quercetin derivatives: From redox properties to promising treatment of oxidative stress related diseases[J]. Chem Biol Interact, 2017, 265:36-46. Doi:10.1016/j.cbi.2017.01.019.
MARIA T G,SERENA F,ELEONORA G,et al. Antimicrobial and anti-lipase activity of quercetin and its C2-C16 3-O-acyl-esters[J]. Bioorg Med Chem,2002,10(2): 269-272.
LUCIA M,CLAUDIA C,CLAUDIO M,et al. In vitro evaluation of quercetin-3-O-acyl esters as topical prodrugs[J]. Int J Pharm, 2007,336(2): 257-262.
ZHONG D W, LIU M M, CAO Y, et al. Discovery of metal ions chelator quercetin derivatives with potent anti-HCV activities[J].Molecules, 2015,20(4):6978-6999.
HUANG H, JIA Q, MA J G, et al. Discovering novel quercetin-3-O-amino acid esters as a new class of Src tyrosine kinase inhibitors[J]. Eur J Med Chem,2009,44(5):1982-1988.
WILSON A M, SERGIO L C, QUINTANA R R. Computational study of the structure-free radical scavenging relationship of procyanidins[J]. Food Chem,2014,161:155-161. Doi:10.1016/j.foodchem.2014.03.111.
CALGAROTTO A K, MASO V,JUNIO G C, et al. Antitumor activities of Quercetin and Green Tea in xenografts of human leukemia HL60 cells[J].Sci Rep,2018,8(1):3459. Doi: 10.1038/s41598-018-21516-5.
TAHSIN F K, MARIA V C, MIN-SUNG L E, 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.
DANIHELOVÁ M, VEVERKA M, TURDÍK E,et al. Antioxidant action and cytotoxicity on HeLa and NIH-3T3 cells of new quercetin derivatives[J]. Interdiscip Toxicol,2013,6(4):209-216.