Login Register Cart 0
Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Novel Resveratrol-chalcone Derivatives: Synthesis and Biological Evaluation

Author(s): Yulu Ma, Xi Zheng, Ping Zhu, Bei Liu, Hui Gao, Zewei Mao*, Lijun Zhang and Chunping Wan*

Volume 19, Issue 5, 2019

Page: [424 - 436] Pages: 13

DOI: 10.2174/1389557518666180727165358

Price: $65

Abstract

Introduction: Resveratrol and chalcones are lead compounds with good biological activities.

Method: In this study, a series of novel derivatives (6-38) between resveratrol and chalcone possessing piperazine moiety have been synthesized, and in vitro anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and anti-proliferative effect on a panel of human tumor cell lines (Hela, A549 and SGC7901) by MTT assay were evaluated.

Result: The results demonstrated that the substituents of the NH group of piperazine ring had an obvious influence on biological activities. Especially, compounds 13, 17, 30, 31 and 36 showed good inhibitory effect on the generation of NO compared to dexamethasone. Furthermore, analogs 20, 21, 22 and 25 were found to be the better anti-proliferative effect on 3 human tumor cell lines, which were found to be a better cytotoxic activity to positive control 5-FU. Many compounds displayed low cytotoxic effect on normal cells L02.

Conclusion: Further FACs analysis showed that compounds 20 and 25 significantly induced apoptosis in A549 cell. These derivatives were considered as the potential anti-inflammatory and anti-tumor agents.

Keywords: Resveratrol, chalcone, anti-inflammatory activity, anti-proliferative activity, FACs analysis, inflammation.

« Previous Next »
Graphical Abstract

[1]
Coussens, L.M.; Werb, Z. Inflammation and cancer. Nature, 2002, 420, 860-867.
[2]
Hayashi, S.; Ueno, N.; Murase, A.; Nakagawa, Y.; Takada, J. Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure-activity relationship for anti-inflammatory drug. Eur. J. Med. Chem., 2012, 50, 179-195.
[3]
Haghighatdoost, F.; Hariri, M. Effect of resveratrol on lipid profile: An updated systematic review and meta-analysis on randomized clinical trials. Pharmacol. Res., 2018, 129, 141-150.
[4]
Mániková, D.; Šestáková, Z.; Rendeková, J.; Vlasáková, D.; Lukáčová, P.; Paegle, E.; Arsenyan, P.; Chovanec, M. Resveratrol-Inspired Benzo[b]selenophenes Act as anti-oxidants in yeast. Molecules, 2018, 23, 507.
[5]
Peterson, J.A.; Doughty, H.P.; Eells, A.J.; Johnson, T.A.; Hastings, J.P.; Crowther, C.M.; Andrus, M.B.; Kenealey, J.D. The effects of 4′-esterified resveratrol derivatives on calcium dynamics in breast cancer cells. Molecules, 2017, 22, 1968.
[6]
Ferraz da Costa, D.C.; Fialho, E.; Silva, J.L. Cancer chemoprevention by resveratrol: the p53 tumor suppressor protein as a promising molecular target. Molecules, 2017, 22, 1014.
[7]
Duan, Y.C.; Guan, Y.Y.; Zhai, X.Y.; Ding, L.N.; Qin, W.P.; Shen, D.D.; Liu, X.Q.; Sun, X.D.; Zheng, Y.C.; Liu, H.M. Discovery of resveratrol derivatives as novel LSD1 inhibitors: Design, synthesis and their biological evaluation. Eur. J. Med. Chem., 2017, 126, 246-258.
[8]
Chen, E.; Ge, X.; Xu, F.; Zhang, Y.; Li, Z.; Pan, J.; Song, J.; Dai, Y.; Zhou, J.; Feng, J.; Liang, G. Design, synthesis and biological evaluation of paralleled Aza resveratrol–chalcone compounds as potential anti-inflammatory agents for the treatment of acute lung injury. Bioorg. Med. Chem. Lett., 2015, 25, 2998-3004.
[9]
Wei, Z.Y.; Chi, K.Q.; Yu, Z.K.; Liu, H.Y.; Sun, L.P.; Zheng, C.J.; Piao, H.R. Synthesis and biological evaluation of chalcone derivatives containing aminoguanidine or acylhydrazone moieties. Bioorg. Med. Chem. Lett., 2016, 26, 5920-5925.
[10]
Mao, Z.W.; Zheng, X.; Lin, Y.P.; Qi, Y.; Hu, C.Y.; Wan, C.P.; Rao, G.X. Concise synthesis and biological evaluation of chalcone derivatives bearing N-heterocyclic moieties. Heterocycles, 2016, 92, 1102-1110.
[11]
Lal, K.; Yadav, P.; Kumar, A.; Kumar, A.; Paul, A.K.S. Design, synthesis, characterization, antimicrobial evaluation and molecular modeling studies of some dehydroacetic acid-chalcone-1, 2, 3-triazole hybrids. Bioorg. Chem., 2018, 77, 236-244.
[12]
Syam, S.; Abdelwahab, S.I.; Al-Mamary, M.A.; Mohan, S. Synthesis of chalcones with anticancer activities. Molecules, 2012, 17, 6179-6195.
[13]
Lin, Y.P.; Hu, C.Y.; Zheng, X.; Wang, X.L.; Wan, C.P.; Mao, Z.W. Synthesis and anti-tumor activities of novel 4′-(N-Substitued-1-piperazinyl)chalcone Derivatives. Chin. J. Org. Chem., 2017, 37, 237-241.
[14]
Ma, Y.; Zheng, X.; Gao, H.; Wan, C.; Rao, G.; Mao, Z. Design, synthesis, and biological Evaluation of novel benzofuran derivatives bearing N-aryl piperazine moiety. Molecules, 2016, 21, 1684.
[15]
Mao, Z.W.; Zheng, X.; Lin, Y.P.; Hu, C.Y.; Wang, X.L.; Wan, C.P.; Rao, G.X. Design, synthesis and anticancer activity of novel hybrid compounds between benzofuran and N-aryl piperazine. Bioorg. Med. Chem. Lett., 2016, 26, 3421-3424.
[16]
Mao, Z.W.; Zheng, X.; Qi, Y.; Zhang, M.D.; Huang, Y.; Wan, C.P.; Rao, G.X. Synthesis and biological evaluation of novel hybrid compounds between chalcone and piperazine as potential antitumor agents. RSC Adv, 2016, 6, 7723-7727.
[17]
Nepali, K.; Sharma, S.; Sharma, M.; Bedi, P.M.S.; Dhar, K.L. Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur. J. Med. Chem., 2014, 77, 422-487.
[18]
Pingaewa, A.; Saekee, A.; Mandi, P.; Nantsenamat, S.; Prachayasittikul, S.; Ruchirawat, S.; Prachayasittikul, V. Synthesis, biological evaluation and molecular docking of novel chalcone–coumarin hybrids as anticancer and antimalarial agents. Eur. J. Med. Chem., 2014, 85, 65-76.
[19]
Gao, H.; Zheng, X.; Qi, Y.; Wang, S.; Wan, C.P.; Rao, G.X.; Mao, Z.W. Synthesis and cytotoxic activity of novel resveratrol-chalcone amide derivatives. Chin. J. Org. Chem., 2018, 38, 648-655.

Rights & Permissions Print Cite
Article Metrics
41
9
1
© 2024 Bentham Science Publishers | Privacy Policy