Citation: Jung Jong-Woon, Damodar Kongara, Kim Jin-Kyung, Jun Jong-Gab. First synthesis and in vitro biological assessment of isosideroxylin, 6, 8-dimethylgenistein and their analogues as nitric oxide production inhibition agents[J]. Chinese Chemical Letters, ;2017, 28(5): 1114-1118. doi: 10.1016/j.cclet.2016.12.041 shu

First synthesis and in vitro biological assessment of isosideroxylin, 6, 8-dimethylgenistein and their analogues as nitric oxide production inhibition agents

a.
Department of Chemistry and Institute of Applied Chemistry, Hallym University, Chuncheon 24252, South Korea
b.
Department of Biomedical Science, College of Natural Science, Catholic University of Daegu, Gyeungsan-Si 38430, South Korea

Corresponding author: Jun Jong-Gab, jgjun@hallym.ac.kr
Received Date: 31 October 2016
Revised Date: 6 December 2016
Accepted Date: 14 December 2016
Available Online: 8 May 2017

Figures(4)

A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin (1), 6, 8-dimethylgenistein (2) and their analogues (3-8) is established for the first time. The synthesis is realized in 7-8 steps in overall yields of 16%-24% from commercially inexpensive phloroglucinol and features a high yielding Vilsmeier-Haack reaction, Friedel-Crafts acylation, Gammill's protocol and Suzuki coupling as the pivotal transformations. Next, these compounds evaluated for their inhibitory potency on the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW-264.7 cells as an indicator of anti-inflammatory activity. The results showed that all the compounds decreased NO production in a dose-dependent manner without marked cytotoxicity and IC₅₀ values are found in the range of 10.17-33.88 μmol/L. Of note, compounds 3 followed by 1, 7 and 8 show comparable inhibitory activity with positive control (N-monomethyl-_L-arginine, L-NMMA).
- Isosideroxylin,
- 6, 8-Dimethylgenistein,
- Vilsmeier-Haack reaction,
- Suzuki coupling,
- Nitric oxide (NO),
- Anti-inflammatory
1. [1]
  J.N. Fullerton, D.W. Gilroy. Resolution of inflammation:a new therapeutic frontier[J]. Nat. Rev. Drug Discov., 2016,15:551-567. doi: 10.1038/nrd.2016.39
2. [2]
  C. Bogdan. Nitric oxide and the immune response[J]. Nat. Immunol., 2001,2:907-916. doi: 10.1038/ni1001-907
3. [3]
  (a) A. J. Duncan, S. J. R. Heales, Nitric oxide and neurological disorders, Mol. Aspects Med. 26(2005) 67-96;
  (b) K. Bian, F. Murad, Nitric oxide (NO)-biogeneration, regulation, and relevance to human diseases, Front Biosci. 8(2003) d264-d278.
4. [4]
  E.R. Gilbert, D. Liu. Anti-diabetic functions of soy isoflavone genistein:mechanisms underlying its effects on pancreatic b-cell function[J]. Food Funct., 2013,4:200-212. doi: 10.1039/C2FO30199G
5. [5]
  (a) J. Yu, X. Bi, B. Yu, D. Chen, Isoflavones: anti-inflammatory benefit and possible caveats, Nutrients 8(2016) 361;
  (b) B. H. Kim, E. Y. Chung, B. -K. Min, et al. , Anti-inflammatory action of legume isoflavonoid sophoricoside through inhibition on cyclooxygenase-2 activity, Planta Med. 69(2003) 474-476.
6. [6]
  (a) C. E. Rüfer, S. E. Kulling, Antioxidant activity of isoflavones and their major metabolites using different in vitro assays, J. Agric. Food Chem. 54(2006) 2926-2931;
  (b) C. H. Lee, L. Yang, J. Z. Xu, et al. , Relative antioxidant activity of soybean isoflavones and their glycosides, Food Chem. 90(2005) 735-741.
7. [7]
  (a) S. Andres, K. Abraham, K. E. Appel, A. Lampen, Risks and benefits of dietary isoflavones for cancer, Crit. Rev. Toxicol. 41(2011) 463-506;
  (b) Y. Kwon, Effect of soy isoflavones on the growth of human breasttumors: findings from preclinical studies, Food Sci. Nutr. 2(2014) 613-622.
8. [8]
  A. Andres, S.M. Donovan, M.S. Kuhlenschmidt. Soy isoflavones and virus infections[J]. J. Nutr. Biochem., 2009,20:563-569. doi: 10.1016/j.jnutbio.2009.04.004
9. [9]
  R.P. Krämer, H. Hindorf, H.C. Jha. Antifungal activity of soybean and chickpea isoflavones and their reduced derivatives[J]. Phytochemistry, 1984,23:2203-2205. doi: 10.1016/S0031-9422(00)80520-8
10. [10]
  (a) C. Morel, F. R. Stermitz, G. Tegos, K. Lewis, Isoflavones as potentiators of antibacterial activity, J. Agric. Food Chem. 51(2003) 5677-5679;
  (b) M. Sato, H. Tanaka, N. Tani, et al. , Different antibacterial actions of isoflavones isolated from Erythrina poeppigiana against methicillin-resistant Staphylococcus aureus, Lett. Appl. Microbiol. 43(2006) 243-248.
11. [11]
  S.D. Varma, I. Mikuni, J.H. Kinoshita. Flavonoids as inhibitors of lens aldose reductase[J]. Science, 1975,188:1215-1216. doi: 10.1126/science.1145193
12. [12]
  G.W. Moersch, D.F. Morrow, W.A. Neuklis. The antifertility activity of isoflavones related to genistein[J]. J. Med. Chem., 1967,10:154-158. doi: 10.1021/jm00314a005
13. [13]
  H. Ogawara, T. Akiyama, S.I. Watanabe. Inhibition of tyrosine protein kinase activity by synthetic isoflavones and flavones[J]. J. Antibiot., 1989,42:340-343. doi: 10.7164/antibiotics.42.340
14. [14]
  A. Ørgaard, L. Jensen. The effects of soy isoflavones on obesity[J]. Exp. Biol. Med., 2008,233:1066-1080. doi: 10.3181/0712-MR-347
15. [15]
  (a) T. Marugame, K. Katanoda, International comparisons of cumulative risk of breast and prostate cancer, from cancer incidence in five continents Vol. Ⅷ, Jpn. J. Clin. Oncol. 36(2006) 399-400;
  (b) A. H. Wu, R. G. Ziegler, A. ]M. Y. Nomura, et al. , Soy intake and risk of breast cancer in Asians and Asian Americans, Am. J. Clin. Nutr. 68(1998) 1437S-1443S; (c) S. Medjakovic, M. Mueller, A. Jungbauer, Potential health-modulating effects of isoflavones and metabolites via activation of PPAR and AhR, Nutrients 2(2010) 241-279.
16. [16]
  (a) K. Damodar, J. K. Kim, J. G. Jun, Synthesis and pharmacological properties of naturally occurring prenylated and pyranochalcones as potent antiinflammatory agents, Chin. Chem. Lett. 27(2016) 698-702;
  (b) Y. H. Seo, K. Damodar, J. K. Kim, J. G. Jun, Synthesis and biological evaluation of 2-aroylbenzofurans, rugchalcones A B and their derivatives as potent antiinflammatory agents, Bioorg. Med. Chem. Lett. 26(2016) 1521-1524.
17. [17]
  D. Tian, J.R. Porter. An isoflavone from Leiophyllum buxifolium and its antiproliferative effect[J]. J. Nat. Prod., 2015,78:1748-1751. doi: 10.1021/acs.jnatprod.5b00100
18. [18]
  A.I. Calderón, C. Terreaux, K. Schenk. Isolation and structure elucidation of an isoflavone and a sesterterpenoic acid from Henriettella fascicularis[J]. J. Nat. Prod., 2002,65:1749-1753. doi: 10.1021/np0201164
19. [19]
  R.B. Gammill. A new and efficient synthesis of 3-halogenated 4H-1-benzopyran-4-ones[J]. Synthesis, 1979:901-903.
20. [20]
  (a) C. Dittmer, G. Raabe, L. Hintermann, Asymmetric cyclization of 2'-hydroxychalcones to flavanones: catalysis by chiral Brønsted acids and bases, Eur. J. Org. Chem. (2007) 5886-5898;
  (b) L. Shi, X. E. Feng, J. R. Cui, et al. , Synthesis and biological activity of flavanone derivatives, Bioorg. Med. Chem. Lett. 20(2010) 5466-5468.
21. [21]
  S. Balasubramanian, M.G. Nair. An efficient 'one pot' synthesis of isoflavones[J]. Synth. Commun., 2000,30:469-484. doi: 10.1080/00397910008087343
22. [22]
  D. Giustarini, R. Rossi, A. Milzani, I. Dalle-Donne, Nitrite and nitrate measurement by Griess reagent in human plasma: Evaluation of interferences and standardization, in: E. Cadenas, L. Packer (Eds. ), Methods in Enzymology, Elsevier Inc. , Richmond, 2008, pp. 361-380.
23. [23]
  (a) L. Salerno, V. Sorrenti, C. Di Giacomo, G. Romeo, M. A. Siracusa, Progress in the development of selective nitric oxide synthase (NOS) inhibitors, Curr. Pharm. Des. 8(2002) 177-200;
  (b) J. L. Song, Y. Yuan, H. B. Tan, et al. , Euryachins A and B, a new type of diterpenoids from Eurya chinensis with potent NO production inhibitory activity, RSC Adv. 6(2016) 85958-85961;
  (c) C. A. Kontogiorgis, D. Hadjipavlou-Litina, Current trends in QSAR on NO donors and inhibitors of nitric oxide synthase (NOS), Med. Res. Rev. 22(2002) 385-418.
1. [1]
  Chaozheng He , Jia Wang , Ling Fu , Wei Wei . Nitric oxide assists nitrogen reduction reaction on 2D MBene: A theoretical study. Chinese Chemical Letters, 2024, 35(5): 109037-. doi: 10.1016/j.cclet.2023.109037
2. [2]
  Xiaoyao Ma , Jinling Zhang , Ge Fang , He Gao , Jie Gao , Li Fu , Yuanyuan Hou , Gang Bai . Förster resonance energy transfer reveals phillygenin and swertiamarin concurrently target AKT on different binding domains to increase the anti-inflammatory effect. Chinese Chemical Letters, 2024, 35(5): 108823-. doi: 10.1016/j.cclet.2023.108823
3. [3]
  Wenjia Wang , Xingyue He , Xiaojie Wang , Tiantian Zhao , Osamu Muraoka , Genzoh Tanabe , Weijia Xie , Tianjiao Zhou , Lei Xing , Qingri Jin , Hulin Jiang . Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin (Ⅳ) prodrug delivery and enhanced colorectal cancer therapy. Chinese Chemical Letters, 2024, 35(4): 108656-. doi: 10.1016/j.cclet.2023.108656
4. [4]
  Xiongbo Song , Jinwen Xiao , Juan Wu , Li Sun , Long Chen . Decellularized amniotic membrane promotes the anti-inflammatory response of macrophages via PI3K/AKT/HIF-1α pathway. Chinese Chemical Letters, 2025, 36(1): 109844-. doi: 10.1016/j.cclet.2024.109844
5. [5]
  Hao Cai , Xiaoyan Wu , Lei Jiang , Feng Yu , Yuxiang Yang , Yan Li , Xian Zhang , Jian Liu , Zijian Li , Hong Bi . Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy. Chinese Chemical Letters, 2024, 35(4): 108946-. doi: 10.1016/j.cclet.2023.108946
6. [6]
  Baokang Geng , Xiang Chu , Li Liu , Lingling Zhang , Shuaishuai Zhang , Xiao Wang , Shuyan Song , Hongjie Zhang . High-efficiency PdNi single-atom alloy catalyst toward cross-coupling reaction. Chinese Chemical Letters, 2024, 35(7): 108924-. doi: 10.1016/j.cclet.2023.108924
7. [7]
  Mengli Xu , Zhenmin Xu , Zhenfeng Bian . Achieving Ullmann coupling reaction via photothermal synergy with ultrafine Pd nanoclusters supported on mesoporous TiO2. Chinese Journal of Structural Chemistry, 2024, 43(7): 100305-100305. doi: 10.1016/j.cjsc.2024.100305
8. [8]
  Xiaofei NIU , Ke WANG , Fengyan SONG , Shuyan YU . Self-assembly of [Pd₆(L)₄]⁸⁺-type macrocyclic complexes for fluorescent sensing of HSO₃^-. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1233-1242. doi: 10.11862/CJIC.20240057
9. [9]
  Zhen Liu , Zhi-Yuan Ren , Chen Yang , Xiangyi Shao , Li Chen , Xin Li . Asymmetric alkenylation reaction of benzoxazinones with diarylethylenes catalyzed by B(C₆F₅)₃/chiral phosphoric acid. Chinese Chemical Letters, 2024, 35(5): 108939-. doi: 10.1016/j.cclet.2023.108939
10. [10]
  Hui Peng , Xiao Wang , Weiguo Huang , Shuiyue Yu , Linghang Kong , Qilin Wei , Jialong Zhao , Bingsuo Zou . Efficient tunable visible and near-infrared emission in Sb³⁺/Sm³⁺-codoped Cs₂NaLuCl₆ for near-infrared light-emitting diode, triple-mode fluorescence anti-counterfeiting and information encryption. Chinese Chemical Letters, 2024, 35(11): 109462-. doi: 10.1016/j.cclet.2023.109462
11. [11]
  Xinlong Han , Huiying Zeng , Chao-Jun Li . Trifluoromethylative homo-coupling of carbonyl compounds. Chinese Chemical Letters, 2025, 36(1): 109817-. doi: 10.1016/j.cclet.2024.109817
12. [12]
  Ke-Ai Zhou , Lian Huang , Xing-Ping Fu , Li-Ling Zhang , Yu-Ling Wang , Qing-Yan Liu . Fluorinated metal-organic framework for methane purification from a ternary CH4/C2H6/C3H8 mixture. Chinese Journal of Structural Chemistry, 2023, 42(11): 100172-100172. doi: 10.1016/j.cjsc.2023.100172
13. [13]
  Qijun Tang , Wenguang Tu , Yong Zhou , Zhigang Zou . High efficiency and selectivity catalyst for photocatalytic oxidative coupling of methane. Chinese Journal of Structural Chemistry, 2023, 42(12): 100170-100170. doi: 10.1016/j.cjsc.2023.100170
14. [14]
  Kongchuan Wu , Dandan Lu , Jianbin Lin , Ting-Bin Wen , Wei Hao , Kai Tan , Hui-Jun Zhang . Elucidating ligand effects in rhodium(Ⅲ)-catalyzed arene–alkene coupling reactions. Chinese Chemical Letters, 2024, 35(5): 108906-. doi: 10.1016/j.cclet.2023.108906
15. [15]
  Shengkai Li , Yuqin Zou , Chen Chen , Shuangyin Wang , Zhao-Qing Liu . Defect engineered electrocatalysts for C–N coupling reactions toward urea synthesis. Chinese Chemical Letters, 2024, 35(8): 109147-. doi: 10.1016/j.cclet.2023.109147
16. [16]
  Xin Huang , Yi Zhao , Wanzhen Liang . Vibronic coupling effect on intersystem crossing rates of TADF emitters. Chinese Journal of Structural Chemistry, 2024, 43(6): 100278-100278. doi: 10.1016/j.cjsc.2024.100278
17. [17]
  Jian Ji , Jie Yan , Honggen Peng . Modulation of dinuclear site by orbital coupling to boost catalytic performance. Chinese Journal of Structural Chemistry, 2024, 43(8): 100360-100360. doi: 10.1016/j.cjsc.2024.100360
18. [18]
  Yuehai Zhi , Chen Gu , Huachao Ji , Kang Chen , Wenqi Gao , Jianmei Chen , Dafeng Yan . The advanced development of innovative photocatalytic coupling strategies for hydrogen production. Chinese Chemical Letters, 2025, 36(1): 110234-. doi: 10.1016/j.cclet.2024.110234
19. [19]
  Haiyang Gu , Xiang Xu . Multicolor hybrid metal halides and anti-counterfeiting. Chinese Journal of Structural Chemistry, 2024, 43(9): 100352-100352. doi: 10.1016/j.cjsc.2024.100352
20. [20]
  Xinyi Hu , Riguang Zhang , Zhao Jiang . Depositing the PtNi nanoparticles on niobium oxide to enhance the activity and CO-tolerance for alkaline methanol electrooxidation. Chinese Journal of Structural Chemistry, 2023, 42(11): 100157-100157. doi: 10.1016/j.cjsc.2023.100157

Get Citation

PDF

XML

Metrics

PDF Downloads(2)
Abstract views(685)
HTML views(39)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142