Synthesis and biological evaluation of quercetin and resveratrol peptidyl derivatives as potential anticancer and antioxidant agents
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Quercetin and resveratrol are polyphenolic compounds, members of the flavonoid and the stilbene family, respectively, both medicinally important as dietary anticancer and antioxidant agents. They are present in a variety of foods—including fruits, vegetables, tea, wine, as well as other dietary supplements—and are responsible for various health benefits. Different quercetin and resveratrol esters of Leu/Met-enkephalin and tetrapeptide Leu-Ser-Lys-Leu (LSKL) were synthesized as model systems for monitoring the influence of the peptides on biological activity of resveratrol and quercetin. General formula of the main peptidyl-quercetin derivatives is 2-[3-(aa)n-4-hydroxyphenyl]-3,5,7-tri-hydroxy-4H-1-benzopyran-4-on, and the general formula of the main peptidyl-resveratrol derivatives is (E)-5-[4-(aa)n)styryl]benzene-1,3-diol. The antioxidant and anticancer activities of prepared compounds were investigated. Significant anticancer activity was obtained for the LSKL-based both quercetin and resveratrol derivatives. All prepared compounds exhibit antioxidant activity, in particular quercetin derivative containing Met-enkephalin.
KeywordsLeucine enkephalin Methionine enkephalin Tetrapeptide LSKL Resveratrol Quercetin
Authors gratefully acknowledge the contribution by the Ministry of Science, Education and Sports of Croatia grant No. 098-0982933-2936. The authors thank Dr. M. Kralj, I. Martin-Kleiner and A. M. Mikecin for evaluating of antiproliferative activity and for useful suggestions. The authors thank Mrs. L. Brkljačić for conduction of HPLC–MS–DPPH measurements. The authors thank also Prof. M. Cudic and Dr. M. Rodriguez for useful suggestions and comments.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
- Baczko I, Liknes D, Yang W, Hamming KC, Searle G, Jaeger K, Husti Z, Juhasz V, Klausz G, Pap R, Saghy L, Varro A, Dolinsky V, Wang S, Rauniyar V, Hall D, Dyck JRB, Light PE (2014) Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation. Br J Pharmacol 171:92–106. https://doi.org/10.1111/bph.12409 CrossRefPubMedGoogle Scholar
- Bourd-Boittin K, Bonnier D, Leyme A, Mari B, Tuffery P, Samson M, Ezan F, Baffet G, Theret N (2011) Protease profiling of liver fibrosis reveals the ADAM metallopeptidase with thrombospondin type 1 motif, 1 as a central activator of transforming growth factor beta. Hepatol 54:2173–2184. https://doi.org/10.1002/hep.24598 CrossRefGoogle Scholar
- Çaylak E, Halıfeoğlu İ, Aydin S, Telo S, Bulmus O, Çelık H (2007) The effects of sulfur-containing compounds on total antioxidant capacity levels of liver, kidney and brain in lead-exposed rats. Turk Klin J Med Sci 27:823–828Google Scholar
- Frombaum M, Le Clanche S, Bonnefont-Rousselot D, Borderie D (2012) Antioxidant effects of resveratrol and other stilbene derivatives on oxidative stress and ˙NO bioavailability: potential benefits to cardiovascular diseases. Biochimie 94:269–276. https://doi.org/10.1016/j.biochi.2011.11.001 CrossRefPubMedGoogle Scholar
- Kellici TF, Chatziathanasiadou MV, Lee M-S, Sayyad N, Geromichalou EG, Vrettos EI, Tsiailanis AD, Chi S-W, Geromichalos GD, Mavromoustakos T, Tzakos AG (2017) Rational design and structure–activity relationship studies of quercetin–amino acid hybrids targeting the anti-apoptotic protein Bcl-xL. Org Biomol Chem 15:7956–7976. https://doi.org/10.1039/c7ob02045g CrossRefPubMedGoogle Scholar
- Sato A, Okada M, Shibuya K, Watanabe E, Seino S, Suzuki K, Narita Y, Shibui S, Kayama T, Kitanaka C (2013) Resveratrol promotes proteasome-dependent degradation of Nanog via p53 activation and induces differentiation of glioma stem cells. Stem Cell Res 11:601–610. https://doi.org/10.1016/j.scr.2013.04.004 CrossRefPubMedGoogle Scholar
- Shi X, Zhao Y, Jiao Y, Shi T, Yang X (2013) ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 cells. PLoS One 8(5):e64266. https://doi.org/10.1371/journal.pone.0064266 CrossRefPubMedPubMedCentralGoogle Scholar
- Stephen H, Wrzesinski SF, Wan YY, Flavell RA (2007) Transforming growth factor-β and the immune response: implications for anticancer therapy. Clin Cancer Res 13:2007Google Scholar
- Yamashiro D, Li CH (1972) Preparation of Nα-Boc-Nε-p-Brz-lysine and Nα-Boc-O-m-BrBzl-tyrosine and their use for the solid phase synthesis of an octapeptide occuring in the HGH molecule. Int J Pept Protein Res 4:181–185. https://doi.org/10.1111/j.1399-3011.1972.tb03418.x CrossRefPubMedGoogle Scholar