Novel quercetin derivatives: synthesis and screening for anti-oxidant activity and aldose reductase inhibition
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Miroslav Veverka
,
Ján Gallovič
Abstract
The direct acylation of quercetin (I) with 3-chloro-2,2-dimethylpropanoyl chloride (II) gives a complex reaction mixture. The synthesis of different acylated quercetin with from mono- to tetra-O-substituted functions was achieved in a simple procedure wherein the yield of isomers depended on the stoichiometric ratio of reagents. The crude reaction mixtures were analysed (LC-MS) and compared with the isolated products. Unambiguous structural characterisation of isomeric quercetin derivatives was confirmed by NMR analysis. In addition, the quercetin dimer can be obtained in a high yield in the simple procedure. The anti-oxidant activity and aldose reductase inhibition of the compounds were screened with the aim of providing bi-functional remedies to treat diabetic complications and other diseases where oxidative stress and the polyol pathway are key etiological factors.
[1] Blois, M. S. (1958). Antioxidant determinations by the use of a stable free radical. Nature, 181, 1199–2000. DOI: 10.1038/1811199a0. http://dx.doi.org/10.1038/1811199a010.1038/1811199a0Search in Google Scholar
[2] Bouktaib, M., Lebrun, S., Atmani, A., & Rolando, C. (2002). Hemisynthesis of all the O-monomethylated analogues of quercetin including the major metabolites, through selective protection of phenolic functions. Tetrahedron, 58, 10001–10009. DOI: 10.1016/s0040-4020(02)01306-6. http://dx.doi.org/10.1016/S0040-4020(02)01306-610.1016/S0040-4020(02)01306-6Search in Google Scholar
[3] Chervyakovsky, E. M., Bolibrukh, D. A., Kurovskii, D. L., Gilep, A. A., Vlasova, T. M., Kurchenko, V. P., & Usanov, S. A. (2008). Oligomeric oxidation products of the flavonoid quercetin. Chemistry of Natural Compounds, 44, 427–431. DOI: 10.1007/s10600-008-9092-1. http://dx.doi.org/10.1007/s10600-008-9092-110.1007/s10600-008-9092-1Search in Google Scholar
[4] Costantino, L., Rastelli, G., Gamberini, M. C., Vinson, J. A., Bose, P., Iannone, A., Staffieri, M., Antolini, L., Del Corso, A., Mura, U., & Albasini, A. (1999). 1-Benzopyran-4-one antioxidants as aldose reductase inhibitors. Journal of Medicinal Chemistry, 42, 1881–1893. DOI: 10.1021/jm980441h. http://dx.doi.org/10.1021/jm980441h10.1021/jm980441hSearch in Google Scholar
[5] Coudert, P., Albuisson, E, Boire, J. Y., Duroux, E., Bastide, P., & Couquelet, J. (1994). Synthesis of pyridazine acetic acid derivatives possessing aldose reductase inhibitory activity and antioxidant properties. European Journal of Medicinal Chemistry, 29, 471–477. DOI: 10.1016/0223-5234(94)90074-4. http://dx.doi.org/10.1016/0223-5234(94)90074-410.1016/0223-5234(94)90074-4Search in Google Scholar
[6] Da Settimo, F., Primofiore, G., La Motta, C., Salerno, S., Novellino, E., Greco, G., Lavecchia, A., Laneri, S., & Boldrini, E. (2005). Spirohydantoin derivatives of thiopyrano[2,3-b]pyridin-4(4H)-one as potent in vitro and in vivo aldose reductase inhibitors. Bioorganic & Medicinal Chemistry, 13, 491–499. DOI: 10.1016/j.bmc.2004.10.019. http://dx.doi.org/10.1016/j.bmc.2004.10.01910.1016/j.bmc.2004.10.019Search in Google Scholar
[7] Furusawa, M., Tsuchiya, H., Nagayama, M., Tanaka, T., Oyama, M., Ito, T., Iinuma, M., & Takeuchi, H. (2006). Cell growth inhibition by membrane-active components in brownish scale of onion. Journal of Health Science, 52, 578–584. DOI: 10.1248/jhs.52.578. http://dx.doi.org/10.1248/jhs.52.57810.1248/jhs.52.578Search in Google Scholar
[8] Golding, B. T., Griffin, R. J., Quarterman, C. P., Slack, J. A., & Williams, J. G. (2001). U.S. Patent No. 6258840 B1. Washington, DC, USA: U.S. Patent and Trademark Office. Search in Google Scholar
[9] Gülşen, A., Makris, D. P., & Kefalas, P. (2007). Biomimetic oxidation of quercetin: Isolation of a naturally occuring quercetin heterodimer and evaluation of its in vitro antioxidant properties. Food Research International, 40, 7–14. DOI: 10.1016/j.foodres.2006.07.009. http://dx.doi.org/10.1016/j.foodres.2006.07.00910.1016/j.foodres.2006.07.009Search in Google Scholar
[10] Harborne, J. B. (Ed.) (1994). The flavonoids, advances in research since 1986 (pp. 378–382). London, UK: Chapman & Hall/CRC. 10.1007/978-1-4899-2911-2Search in Google Scholar
[11] Harborne, J. B., & Williams, C. A. (2000). Advances in flavonoid research since 1992. Phytochemistry, 55, 481–504. DOI: 10.1016/s0031-9422(00)00235-1. http://dx.doi.org/10.1016/S0031-9422(00)00235-110.1016/S0031-9422(00)00235-1Search in Google Scholar
[12] Hayman, S., & Kinoshita, J. H. (1965). Isolation and properties of lens aldose reductase. The Journal of Biological Chemistry, 240, 877–882. 10.1016/S0021-9258(17)45256-2Search in Google Scholar
[13] Jurd, L. (1962). The selective alkylation of polyphenols. II. Methylation of 7-, 4′-, and ′-hydroxyl groups in flavonols. The Journal of Organic Chemistry, 27, 1294–1297. DOI: 10.1021/jo01051a041. http://dx.doi.org/10.1021/jo01051a04110.1021/jo01051a041Search in Google Scholar
[14] Jurd, L. (1972). U.S. Patent No. 3661890. Washington, DC, USA: U.S. Patent and Trademark Office. Search in Google Scholar
[15] Kim, B. H., Yoo, J., Park, S. H., Jung, J. K., Cho, H., & Chung, Y. (2006). Synthesis and evaluation of antitumor activity of novel 1,4-naphthoquinon derivatives (IV). Archives of Pharmacal Research, 29, 123–130. DOI: 10.1007/bf02974272. http://dx.doi.org/10.1007/BF0297427210.1007/BF02974272Search in Google Scholar PubMed
[16] Krishnamachari, V., Levine, L. H., & Paré, P. W. (2002). Flavonoid oxidation by the radical generator AIBN: A unified mechanism for quercetin radical scavenging. Journal of Agricultural and Food Chemistry, 50, 4357–4363. DOI: 10.1021/jf020045e. http://dx.doi.org/10.1021/jf020045e10.1021/jf020045eSearch in Google Scholar PubMed
[17] La Motta, C., Sartini, S., Mugnaini, L., Simorini, F., Taliani, S., Salerno, S., Marini, A. M., Da Settimo, F., Lavecchia, A., Novellino, E., Cantore, M., Failli, P., & Ciuffi, M. (2007). Pyrido[1,2-a]pyrimidin-4-one derivatives as a novel class of selective aldose reductase inhibitors exhibiting antioxidant activity. Journal of Medicinal Chemistry, 50, 4917–4927. DOI: 10.1021/jm070398a. http://dx.doi.org/10.1021/jm070398a10.1021/jm070398aSearch in Google Scholar PubMed
[18] Li, N. G., Shi, Z. H., Tang, Y. P., Yang, J. P., & Duan, J. A. (2009). An efficient partial synthesis of 4′-O-methylquercetin via regioselective protection and alkylation of quercetin. Beilstein Journal of Organic Chemistry, 5, No. 60. DOI: 10.3762/bjoc.5.60. 10.3762/bjoc.5.60Search in Google Scholar PubMed PubMed Central
[19] Lin, Y. M. (2001). WO Patent No. 200121164. Geneva, Switzerland: World Intellectual Property Organization. Search in Google Scholar
[20] Materska, M. (2008). Quercetin and its derivatives: chemical structure and bioactivity — a rewiev. Polish Journal of Food and Nutrition Sciences, 58, 407–413. Search in Google Scholar
[21] Mattarei, A., Biasutto, L., Rastrelli, F., Garbisa, S., Marotta, E., Zoratti, M., & Paradisi, C. (2010). Regioselective Oderivatization of quercetin via ester intermediates. An improved synthesis of rhamnetin and development of a new mitochondriotropic derivative. Molecules, 15, 4722–4736. DOI: 10.3390/molecules15074722. http://dx.doi.org/10.3390/molecules1507472210.3390/molecules15074722Search in Google Scholar PubMed PubMed Central
[22] Moon, B. H., Lee, Y., Shin, C., & Lim, Y. (2005). Complete assignments of the 1H and 13C NMR data of flavone derivatives. Bulletin of the Korean Chemical Society, 26, 603–608. DOI: 10.5012/bkcs.2005.26.4.603. http://dx.doi.org/10.5012/bkcs.2005.26.4.60310.5012/bkcs.2005.26.4.603Search in Google Scholar
[23] Perrier, E., Mariotte, A. M., Boumendjel, A., & Bresson-Rival, D. (2001). U.S. Patent No. 6235294. Washington, DC, USA: U.S. Patent and Trademark Office. Search in Google Scholar
[24] Stefek, M., Snirc, V., Djoubissie, P. O., Majekova, M., Demopoulos, V., Rackova, L., Bezakova, Z., Karasu, C., Carbone, V., & El-Kabbani, O. (2008). Carboxymethylated pyridoindole antioxidants as aldose reductase inhibitors: Synthesis, activity, partitioning, and molecular modeling. Bioorganic & Medicinal Chemistry, 16, 4908–4920. DOI: 10.1016/j.bmc.2008.03.039. http://dx.doi.org/10.1016/j.bmc.2008.03.03910.1016/j.bmc.2008.03.039Search in Google Scholar PubMed
[25] Tandon, V. K., Maurya, H. K., Mishra, N. N., & Shukla, P. K. (2009). Design, synthesis and biological evaluation of novel nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents. European Journal of Medicinal Chemistry, 44, 3130–3137. DOI: 10.1016/j.ejmech.2009.03.006. http://dx.doi.org/10.1016/j.ejmech.2009.03.00610.1016/j.ejmech.2009.03.006Search in Google Scholar PubMed
[26] Zenkevich, I. G., Eshchenko, A. Y., Makarova, S. V., Vitenberg, A. G., Dobryakov, Y. G., & Utsal, V. A. (2007). Identification of the products of oxidation of quercetin by air oxygen at ambient temperature. Molecules, 12, 654–672. DOI: 10.3390/12030654. http://dx.doi.org/10.3390/1203065410.3390/12030654Search in Google Scholar PubMed PubMed Central
© 2012 Institute of Chemistry, Slovak Academy of Sciences
Articles in the same Issue
- Professor Dr. Štefan Toma—excellent scientist and teacher—celebrates his 75th birthday
- Palladium-catalysed Claisen rearrangement of 6-allyloxypurines
- Applicability of photochemically generated pendant benzoyl peroxides in both “grafting from” and “grafting to” techniques
- Spectral characterisation of new organic fluorescent dyes with an alkoxysilane moiety and their utilisation for the labelling of layered silicates
- Substituted homoallenyl aldehydes and their derivatives. Part 1: Homoallenyl aldehydes and protected hydrazones
- Substituted homoallenyl aldehydes and their derivatives. Part 2: Azines
- Methyltrioxorhenium-catalysed oxidation of secondary amines to nitrones in ionic liquids
- Thiophenium-ylides: Synthesis and reactivity
- Aminohydroxylation of divinylcarbinol and its application to the synthesis of bicyclic hydroxypyrrolidine and aminotetrahydrofuran building blocks
- Novel quercetin derivatives: synthesis and screening for anti-oxidant activity and aldose reductase inhibition
- Total synthesis of N,O,O,O-tetraacetyl-d-ribo-phytosphingosine and its 2-epi-congener
- A concise synthesis of enantiomerically pure aroyl-l-alanines and dihydroaroyl-l-alanines
- Synthesis and properties of macrocyclic diazene switch with binaphthalene unit attached via acrylamide linkers
- Conjugated push-pull salts derived from linear benzobisthiazole: preparation and optical properties
- Effect of reactants’ concentration on the ratio and yield of E,Z isomers of isatin-3-(4-phenyl)semicarbazone and N-methylisatin-3-(4-phenyl)semicarbazone
Articles in the same Issue
- Professor Dr. Štefan Toma—excellent scientist and teacher—celebrates his 75th birthday
- Palladium-catalysed Claisen rearrangement of 6-allyloxypurines
- Applicability of photochemically generated pendant benzoyl peroxides in both “grafting from” and “grafting to” techniques
- Spectral characterisation of new organic fluorescent dyes with an alkoxysilane moiety and their utilisation for the labelling of layered silicates
- Substituted homoallenyl aldehydes and their derivatives. Part 1: Homoallenyl aldehydes and protected hydrazones
- Substituted homoallenyl aldehydes and their derivatives. Part 2: Azines
- Methyltrioxorhenium-catalysed oxidation of secondary amines to nitrones in ionic liquids
- Thiophenium-ylides: Synthesis and reactivity
- Aminohydroxylation of divinylcarbinol and its application to the synthesis of bicyclic hydroxypyrrolidine and aminotetrahydrofuran building blocks
- Novel quercetin derivatives: synthesis and screening for anti-oxidant activity and aldose reductase inhibition
- Total synthesis of N,O,O,O-tetraacetyl-d-ribo-phytosphingosine and its 2-epi-congener
- A concise synthesis of enantiomerically pure aroyl-l-alanines and dihydroaroyl-l-alanines
- Synthesis and properties of macrocyclic diazene switch with binaphthalene unit attached via acrylamide linkers
- Conjugated push-pull salts derived from linear benzobisthiazole: preparation and optical properties
- Effect of reactants’ concentration on the ratio and yield of E,Z isomers of isatin-3-(4-phenyl)semicarbazone and N-methylisatin-3-(4-phenyl)semicarbazone
