Login Register Cart 0
Generic placeholder image

Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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

Synthesis and Biological Evaluation of Isofebrifugine Analogues

Author(s): Jinjin Zhang, Baohua Huang*, Yujing Lu, Wenbin Li, Zichong Zhuang, Donghua Ke, Jingpeng Zhong, Jinlin Zhou and Qian Chen

Volume 16, Issue 12, 2019

Page: [1004 - 1010] Pages: 7

DOI: 10.2174/1570178616666190417115639

Price: $65

Abstract

Isofebrifugine, as a kind of natural quinazolinone alkaloid with important physiological activities and good pharmacological effects, was isolated from a Chinese medicinal plant, Chang Shan (Dichroa febrifuga). In this paper, the synthesis of a series of novel isofebrifugine analogues was accomplished by employing the N-alkylation of 4(3H)-quinazolinones with benzyl (3aR,7aR)-rel-2- (bromomethyl)hexahydrofuro[3,2-b]pyridine-4(2H)carboxylates and the subsequent N-deprotection. These analogues were characterized by 1H NMR, 13C NMR and HRMS spectra. The MTT assay was used to examine the inhibitory effects of these analogues on the growth of human hepatoma cells (HepG2). The results indicated that some halogenated or hemiketal analogues showed interesting inhibition activity.

Keywords: Isofebrifugine, analogue, piperidine, quinazolinone, convergent synthesis, HepG2.

Next »
Graphical Abstract

[1]
(a)Koepfli, J.B.; Mead, J.F.; Brockman, J.A., Jr J. Am. Chem. Soc., 1947, 69, 1837.
(b)Kuehl, F.A., Jr; Spencer, C.F.; Folkers, K. J. Am. Chem. Soc., 1948, 70, 2091-2093.
(c)Koepfli, J.B.; Mead, J.F.; Brockman, J.A., Jr J. Am. Chem. Soc., 1949, 71, 1048-1054.
(d)Koepfli, J.B.; Brockman, J.A., Jr; Moffat, J. J. Am. Chem. Soc., 1950, 72, 3323.
(e)Ablondi, F.; Gordon, S.; Morton, J., II; Williams, J.H. J. Org. Chem., 1952, 17, 14-18.
[2]
(a)Wiesner, J.; Ortmann, R.; Jomaa, H.; Schlitzer, M. Angew. Chem. Int. Ed., 2003, 42, 5274-5293.
(b)Mital, A. Curr. Med. Chem., 2007, 14, 759-773.
(c)Kumar, V.; Mahajan, A.; Chibale, K. Bioorg. Med. Chem., 2009, 17, 2236-2275; (c) Şahin, B.; Demir, E.; Aygün, A.; Gündüz, H.; Şen, F. J. Biotechnol., 2017, 260, 79-83.
(d)Şahin, B.; Aygün, A.; Gündüz, H.; Şahin, K.; Demir, E.; Akocak, S.; Şen, F. Colloids Surf. B Biointerfaces, 2018, 163, 119-124.
(e)Gulçin, İ.; Taslimi, P.; Aygün, A.; Sadeghian, N.; Bastem, E.; Kufrevioglu, O.I.; Turkan, F.; Şen, F. Int. J. Biol. Macromol., 2018, 119, 741-746.
[3]
Jiang, S.; Zeng, Q.; Gettayacamin, M.; Tungtaeng, A.; Wannaying, S.; Lim, A.; Hansukjariya, P.; Okunji, C.O.; Zhu, S.; Fang, D. Antimicrob. Agents Chemother., 2005, 49, 1169-1176.
[4]
Ryley, J.F.; Wilson, R.G. Parasitology, 1975, 70, 203-222.
[5]
Baker, B.R.; Schaub, R.E.; McEvoy, F.J.; Williams, J.H. J. Org. Chem., 1952, 17, 132-140.
[6]
Baker, B.R.; McEvoy, F.J. J. Org. Chem., 1955, 20, 136-142.
[7]
Kobayashi, S.; Ueno, M.; Suzuki, R.; Ishitani, H.; Kim, H.S.; Wataya, Y. J. Org. Chem., 1999, 64, 6833-6841.
[8]
Okitsu, O.; Suzuki, R.; Kobayashi, S. J. Org. Chem., 2001, 66, 809-823.
[9]
Takeuchi, Y.; Hattori, M.; Abe, H.; Harayama, T. Synthesis, 1999, 1814-1818.
[10]
Takeuchi, Y.; Koike, M.; Azuma, K.; Nishioka, H.; Abe, H.; Kim, H-S.; Wataya, Y.; Harayama, T. Chem. Pharm. Bull. , 2001, 49, 721-725.
[11]
Nagler, A.; Firman, N.; Feferman, R.; Cotev, S.; Pines, M.; Shoshan, S. Am. J. Respir. Crit. Care Med., 1996, 154, 1082-1086.
[12]
Halevy, O.; Nagler, A.; Levi-Schaffer, F.; Genina, O.; Pines, M. Biochem. Pharmacol., 1996, 52, 1057-1063.
[13]
Sundrud, M.S.; Koralov, S.B.; Feuerer, M.; Calado, D.P.; Kozhaya, A.E.; Rhule-Smith, A.; Lefebvre, R.E.; Unutmaz, D.; Mazitschek, R.; Waldner, H.; Whitman, M.; Keller, T.; Rao, A. Science, 2009, 324, 1334-1338.
[14]
de Jonge, M.J.A.; Dumez, H.; Verweij, J.; Yarkoni, S.; Snyder, D.; Lacombe, D.; Marréaud, S.; Yamaguchi, T.; Punt, C.J.A.; van Oosterom, A. Eur. J. Cancer, 2006, 42, 1768-1774.
[15]
Kikuchi, H.; Horoiwa, S.; Kasahara, R.; Hariguchi, N.; Matsumoto, M.; Oshima, Y. Eur. J. Med. Chem., 2014, 76, 10-19.
[16]
Kikuchi, H.; Yamamoto, K.; Horoiwa, S.; Hirai, S.; Kasahara, R.; Hariguchi, N.; Matsumoto, M.; Oshima, Y. J. Med. Chem., 2006, 49, 4698-4706.
[17]
Zhu, S.; Chandrashekar, G.; Meng, L.; Robinson, K.; Chatterji, D. Bioorg. Med. Chem., 2012, 20, 927-932.
[18]
Sen, D.; Chatterjee, T.K. J. Adv. Pharm. Technol. Res., 2013, 4, 50-60.
[19]
Baker, B.R.; Schaub, R.E.; Joseph, J.P.; McEvoy, F.J.; Williams, J.H. J. Org. Chem., 1952, 17, 141-148.
[20]
Zhang, J.; Huang, B.; Lu, Y.; Li, W.; Zhuang, Z.; Ke, D.; Zhong, J.; Chen, Q. Isofebrifugine derivatives and their preparation method and application in preparation of antitumor drugs. Faming Zhuanli Shenqing, CN109020985A, December 2018

Rights & Permissions Print Cite
Article Metrics
39
1
© 2024 Bentham Science Publishers | Privacy Policy