Flavones and Related Compounds: Synthesis and Biological Activity

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Sep 28

PMID 37764304

Authors

Denisa Leonte

Daniel Ungureanu

Valentin Zaharia

Affiliations

Soon will be listed here.

Abstract

This review focuses on the synthesis and biological activity of flavones and their related flavonoidic compounds, namely flavonols and aurones. Among the biological activities of natural and synthetic flavones and aurones, their anticancer, antioxidant, and antimicrobial properties are highlighted and detailed in this review. Starting from the structures of natural flavones acting on multiple anticancer targets (myricetin, genkwanin, and other structurally related compounds), new flavone analogs were recently designed and evaluated for their anticancer activity. The most representative compounds and their anticancer activity are summarized in this review. Natural flavones recognized for their antimicrobial properties (baicalein, luteolin, quercetol, apigenin, kaempferol, tricin) have been recently derivatized or structurally modulated by chemical synthetic methods in order to obtain new effective antimicrobial flavonoidic derivatives with improved biological properties. The most promising antimicrobial agents are systematically highlighted in this review. The most applied method for the synthesis of flavones and aurones is based on the oxidative cyclization of -hydroxychalcones. Depending on the reaction conditions and the structure of the precursor, in some cases, several cyclization products result simultaneously: flavones, flavanones, flavonols, and aurones. Based on the literature data and the results obtained by our research group, our aim is to highlight the most promising methods for the synthesis of flavones, as well as the synthetic routes for the other structurally related cyclization products, such as hydroxyflavones and aurones, while considering that, in practice, it is difficult to predict which is the main or exclusive cyclization product of -hydroxychalcones under certain reaction conditions.

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References

Du Z, Ng H, Zhang K, Zeng H, Wang J . Ionic liquid mediated Cu-catalyzed cascade oxa-Michael-oxidation: efficient synthesis of flavones under mild reaction conditions. Org Biomol Chem. 2011; 9(20):6930-3. DOI: 10.1039/c1ob06209c. View

Moreira J, Ribeiro D, Silva P, Nazareth N, Monteiro M, Palmeira A . New Alkoxy Flavone Derivatives Targeting Caspases: Synthesis and Antitumor Activity Evaluation. Molecules. 2019; 24(1). PMC: 6337158. DOI: 10.3390/molecules24010129. View

Nemeth-Rieder A, Keglevich P, Hunyadi A, Latif A, Zupko I, Hazai L . Synthesis and In Vitro Anticancer Evaluation of Flavone-1,2,3-Triazole Hybrids. Molecules. 2023; 28(2). PMC: 9860848. DOI: 10.3390/molecules28020626. View

Sedlacek H, Czech J, Naik R, Kaur G, Worland P, Losiewicz M . Flavopiridol (L86 8275; NSC 649890), a new kinase inhibitor for tumor therapy. Int J Oncol. 2011; 9(6):1143-68. DOI: 10.3892/ijo.9.6.1143. View

Fujimoto K, Nema D, Ninomiya M, Koketsu M, Sadanari H, Takemoto M . An in silico-designed flavone derivative, 6-fluoro-4'-hydroxy-3',5'-dimetoxyflavone, has a greater anti-human cytomegalovirus effect than ganciclovir in infected cells. Antiviral Res. 2018; 154:10-16. DOI: 10.1016/j.antiviral.2018.03.006. View

Seijas J, Vazquez-Tato M, Carballido-Reboredo R . Solvent-free synthesis of functionalized flavones under microwave irradiation. J Org Chem. 2005; 70(7):2855-8. DOI: 10.1021/jo048685z. View

Song G, Ahn B . Synthesis of dibenzoylmethanes as intermediates for flavone synthesis by a modified Baker-Venkataraman rearrangement. Arch Pharm Res. 1994; 17(6):434-7. DOI: 10.1007/BF02979121. View

Lawrence N, Rennison D, McGown A, Hadfield J . The total synthesis of an aurone isolated from Uvaria hamiltonii: aurones and flavones as anticancer agents. Bioorg Med Chem Lett. 2003; 13(21):3759-63. DOI: 10.1016/j.bmcl.2003.07.003. View

Grigalius I, Petrikaite V . Relationship between Antioxidant and Anticancer Activity of Trihydroxyflavones. Molecules. 2017; 22(12). PMC: 6149854. DOI: 10.3390/molecules22122169. View

10.

Singh S, Yap W, Arfuso F, Kar S, Wang C, Cai W . Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?. World J Gastroenterol. 2015; 21(43):12261-73. PMC: 4649111. DOI: 10.3748/wjg.v21.i43.12261. View

11.

Thanigaimalai P, Yang H, Sharma V, Kim Y, Jung S . The scope of thallium nitrate oxidative cyclization of chalcones; synthesis and evaluation of isoflavone and aurone analogs for their inhibitory activity against interleukin-5. Bioorg Med Chem. 2010; 18(12):4441-5. DOI: 10.1016/j.bmc.2010.04.075. View

12.

Spiegel M, Andruniow T, Sroka Z . Flavones' and Flavonols' Antiradical Structure-Activity Relationship-A Quantum Chemical Study. Antioxidants (Basel). 2020; 9(6). PMC: 7346117. DOI: 10.3390/antiox9060461. View

13.

Priyadarshani G, Nayak A, Amrutkar S, Das S, Guchhait S, Kundu C . Scaffold-Hopping of Aurones: 2-Arylideneimidazo[1,2-]pyridinones as Topoisomerase IIα-Inhibiting Anticancer Agents. ACS Med Chem Lett. 2016; 7(12):1056-1061. PMC: 5150667. DOI: 10.1021/acsmedchemlett.6b00242. View

14.

Zhang N, Yang J, Li K, Luo J, Yang S, Song J . Synthesis of Flavone Derivatives via -Amination and Evaluation of Their Anticancer Activities. Molecules. 2019; 24(15). PMC: 6695693. DOI: 10.3390/molecules24152723. View

15.

Meguellati A, Ahmed-Belkacem A, Yi W, Haudecoeur R, Crouillere M, Brillet R . B-ring modified aurones as promising allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase. Eur J Med Chem. 2014; 80:579-92. DOI: 10.1016/j.ejmech.2014.04.005. View

16.

Ross J, Kasum C . Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr. 2002; 22:19-34. DOI: 10.1146/annurev.nutr.22.111401.144957. View

17.

French K, Schrecengost R, Lee B, Zhuang Y, Smith S, Eberly J . Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res. 2003; 63(18):5962-9. View

18.

Toth S, Szepesi A, Tran-Nguyen V, Sarkadi B, Nemet K, Falson P . Synthesis and Anticancer Cytotoxicity of Azaaurones Overcoming Multidrug Resistance. Molecules. 2020; 25(3). PMC: 7038029. DOI: 10.3390/molecules25030764. View

19.

Zwaagstra M, Timmerman H, van de Stolpe A, de Kanter F, Tamura M, Wada Y . Synthesis and structure-activity relationships of carboxyflavones as structurally rigid CysLT1 (LTD4) receptor antagonists. J Med Chem. 1998; 41(9):1428-38. DOI: 10.1021/jm970179x. View

20.

Li X, Zhang C, Guo S, Rajaram P, Lee M, Chen G . Structure-activity relationship and pharmacokinetic studies of 3-O-substitutedflavonols as anti-prostate cancer agents. Eur J Med Chem. 2018; 157:978-993. PMC: 6245954. DOI: 10.1016/j.ejmech.2018.08.047. View