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ABSTRACT: A series of trans-3-aryl acrylic acids 1-27 and their derivatives 28-34 were prepared and evaluated for their antiviral activity against tobacco mosaic virus (TMV) for the first time. The bioassay results showed that most of these compounds exhibited good antiviral activity against TMV, of which compounds 1, 5, 6, 20, 27 and 34 exhibited significantly higher activity against TMV than commercial Ribavirin both in vitro and in vivo. Furthermore, these compounds have more simple structure than commercial Ribavirin, and can be synthesized more efficiently. These new findings demonstrate that trans-3-aryl acrylic acids and their derivatives represent a new template for antiviral studies and could be considered for novel therapy against plant virus infection.
PLoS ONE 01/2013; 8(2):e56475. · 4.09 Impact Factor
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Ti Wen,
Yangguang Li,
Meng Wu,
Xi Chen,
Lin Han,
Xiucong Bao,
Ziwen Wang, Kailiang Wang,
Yanna Hu,
Xinglong Zhou,
Zhenzhou Wu,
Puyue Wang,
Zhangyong Hong,
Liqing Zhao,
Qingmin Wang,
Zhinan Yin
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ABSTRACT: In this study, we synthesized (±)-tylophorine malate (NK-007), an analog of tylophorine (DCB3503), and analyzed its anti-inflammatory effect in vivo using a dextran sulfate sodium (DSS)-induced colitis model and an acetic acid-induced colitis model. As indicated by disease activity index (DAI) and degree of macroscopic colonic damage, NK-007 can significantly suppress colitis. To delineate the underlying mechanism, we have explored the influence of NK-007 on the production of TNF-α by murine primary bone marrow-derived dendritic cells (BMDCs) as well as monocyte/macrophage cell line Raw 264.7 triggered by lipopolysaccharide (LPS). For both types of innate immune cells, NK-007 showed a potent TNF-α inhibitory effect, and has in addition reduced the expression of IL-12 in BMDCs. Moreover, Raw cells treated with NK-007 also showed decreased phosphorylation of NF-κB, which may explain the protective immune-regulatory effect of NK-007 for experimental colitis.
International immunopharmacology 08/2012; 14(4):487-494. · 2.21 Impact Factor
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ABSTRACT: The synthesis of (S)-(+)-tylophorine and its seco analogues has been accomplished by using free radical reaction. (−)-N-(2,3,6,7-Tetramethoxyphenanthren-9-ylmethyl)-2-bromomethylpyrrolidine (7) and (−)-N-(2,3,6,7-tetramethoxyphenanthren-9-ylcarbonyl)-2-bromomethylpyrrolidine (9) have been obtained for the first time in three
and two linear steps from 2,3,6,7-tetramethoxyphenanthrene-9-carboxylic acid (4), respectively. When bromide 7 was subjected
to the action of tri-n-butyltin hydride and catalytic amount of azobisisobutyronitrile in acetonitrile at reflux, only a new structural N-((2,3,6,7-tetrame-thoxyphenanthren-9-yl)methyl)piperidine (2) was obtained in excellent yield, without expected (+)- tylophorine.
As an alternative route, when bromide 9 was treated with azobisisobutyronitrile and tri-n-butyltin hydride in toluene at reflux, tylophorin-9-one (10) was provided in 33.6% yield. At the same time, a new structural
(+)-N-((2,3,6,7-tetramethoxyphenanthren-9-yl)carbonyl)-2-methylpyrrolidine (11) was afforded as the main product in 65% yield.
Notably, azobisisobutyronitrile plays dual roles in this reaction, and the possible mechanism has been described. Compounds
10 and 11 were reduced by lithium aluminum hydride to give (+)-tylophorine and (+)-N-((2,3,6,7-tetramethoxyphenanthren-9-yl) methyl)-2-methylpyrrolidine (3), respectively.
Science in China Series B Chemistry 04/2012; 52(9):1288-1299. · 1.20 Impact Factor
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Ziwen Wang,
Meng Wu,
Yi Wang,
Zheng Li,
Lei Wang,
Guifang Han,
Fazhong Chen,
Yuxiu Liu, Kailiang Wang,
Ao Zhang,
Linghua Meng,
Qingmin Wang
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ABSTRACT: A series of phenanthroindolizidine and phenanthroquinolizidine alkaloids and their 14-amino-derivatives (1-44) were prepared and systematically evaluated for their anti-tumor activities against A549 and HL60 cell lines. The bioassay results showed that most of these alkaloids possess good anti-tumor activities. Especially, compounds 15, 22, 28, 33-36, 40 and 42 displayed low nanomolar or subnanomolar levels of anti-tumor activity. The configuration of (13aS,14S)-14-hydroxyphenanthroindolizidines and (14aR,15R)-15-hydroxyphenanthroquinolizidines was confirmed to be optimal. 14-Amino-phenanthroindolizidines with increased polarity possess good anti-tumor activity, especially for compounds 26 and 28. Most of the phenanthroquinolizidine alkaloids exhibited higher anti-tumor activity than that of phenanthroindolizidine alkaloids. Our present study provides fundamental support for development and optimization of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potential anti-tumor drugs.
European journal of medicinal chemistry 03/2012; 51:250-8. · 3.27 Impact Factor
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ABSTRACT: A series of C9-substituted phenanthrene-based tylophorine derivatives (PBTs) were designed, synthesized, and first evaluated for their antiviral activities against tobacco mosaic virus (TMV). These compounds contain a phenanthrene core structure and can be synthesized some efficiently with excellent yields compared with tylophorine alkaloid. The bioassay results show that some of these compounds exhibited higher antiviral activity against TMV in vivo than tylophorine and commercial Ningnanmycin. Especially, compounds 3, 4, 9, 13, and 16 emerged as potential inhibitors of plant virus. These new findings demonstrate that these phenanthrene-based tylophorine derivatives (PBTs) represent another new template for antiviral studies and could be considered for novel therapy against plant virus infection.
Journal of Agricultural and Food Chemistry 11/2010; · 2.82 Impact Factor
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ABSTRACT: Racemic phenanthroindolizidine alkaloids tylophorine, antofine, and deoxytylophorinine, and optically pure alkaloids S-(+)-tylophorine and R-(-)-tylophorine were synthesized and evaluated for their antiviral activities against tobacco mosaic virus (TMV). Further salinization modifications based on tylophorine increased stability and water solubility and improved the antiviral activity in application. The bioassay results showed that most of these synthesized compounds showed higher antiviral activity against TMV in vitro and in vivo than commercial Ningnanmycin. Especially, tylophorine salt derivatives 10, 11, 13, 17, and 22 emerged as potential inhibitors of plant virus. These findings demonstrate that these phenanthroindolizidine alkaloids and their salt derivatives represent a new template for antiviral studies and could be considered for novel therapy against plant virus infection.
Journal of Agricultural and Food Chemistry 12/2009; 58(5):2703-9. · 2.82 Impact Factor
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Annalen der Chemie und Pharmacie 11/2009; 2010(2):292 - 299. · 3.10 Impact Factor
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ABSTRACT: Easily available and nontoxic FeCl(3) catalyzes intramolecular oxidative coupling for the direct construction of the phenanthrene ring using meta-chloroperbenzoic acid as sole oxidant at room temperature in excellent yields. The mechanistic investigations show that FeCl(3)-catalyzed coupling proceeds through the heterolytic coupling (A(+) + B). The catalytic approach has been applied to intermolecular biaryl coupling of 2-naphthols and phenol ether.
The Journal of Organic Chemistry 01/2009; 74(2):935-8. · 4.45 Impact Factor
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ABSTRACT: Aza-modifications of phenanthroindolizidine and phenanthroquinolizidine alkaloids were firstly designed to produce two aza-analogues, 13a-azatylophorine and 14a-aza-7-methoxylcryptopleurine starting from hydrazine monohydrate with high overall yields, respectively. The synthesis highlighted that some kinds of reactions were ameliorated in methodology. The newly synthesized target molecules including their salt derivatives were evaluated for anticancer activities against the BEL-7402 human liver cancer cell line and MOLT-4 human leukemia cell line. They exhibit anticancer activities.
Letters in Organic Chemistry 06/2008; 5(5):383-390. · 0.82 Impact Factor
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ABSTRACT: Due to the profound cytotoxicities and interesting biochemical aspects, phenanthroindolizidine alkaloids have received attention as potential therapeutic leads. To define the features of the molecule that are essential for their excellent bioactivities, we have synthesized two hexahydropyrrolo[1,2-b]isoquinolines and their hydrochloride salts and picrates concisely and evaluated their antiviral and anticancer activities. We found that the replacement of the phenanthrene with a benzene in phenanthroindolizidine alkaloids observably decreased their antiviral and anticancer activities, and thus the phenanthrene in phenanthroindolizidine alkaloids is essential for high antiviral and anticancer activities.
Letters in Organic Chemistry 02/2008; 5(2):98-102. · 0.82 Impact Factor
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ABSTRACT: A new structural phenanthroindolizidine, 2,3,6,7-tetramethoxyphenanthro[9,10,3',4']indolizidine, has been synthesized efficiently from pyrrole. An important feature of this synthesis is that intramolecular oxidative coupling and rearrangement of 6,7-bis(3,4-dimethoxyphenyl)-8-methoxy-1,2,3-trihydroindolizin-5-one by using VOF3 and TFA have been achieved in one pot.
The Journal of Organic Chemistry 11/2007; 72(22):8416-21. · 4.45 Impact Factor
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ABSTRACT: The first total synthesis of (+)-deoxytylophorinine has been accomplished in 6 linear steps and with 39.6% overall yield. An important feature of this synthesis is that Friedel-Craft acylation of (S)-1- benzyloxycarbonylpyrrolidine-2-acetyl chloride with phenylmethylether catalyzed with fresh anhydrous aluminum chloride to provide 2-(4-methoxyphenacyl)pyrrolidine and cleavage of the Cbz group have been proceeded in one pot. We have found that (+)-deoxytylophorinine shows excellent anti-TMV activity.
Letters in Organic Chemistry 10/2006; 3(11):806-810. · 0.82 Impact Factor
