Broad spectrum anti-RNA virus activities of titanium and vanadium substituted polyoxotungstates

Broad spectrum anti-RNA virus activities of titanium and vanadium substituted polyoxotungstates
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DOI:
10.1016/s0166-3542(03)00009-3
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发表时间:
2003-05-01
期刊:
影响因子:
7.6
通讯作者:
Yamase, T
Yamase, T
中科院分区:
医学2区
文献类型:
--
作者:
Shigeta, S;Mori, S;Yamase, T

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用钒或钛原子取代的七种多钨酸盐检测了它们对黄病毒科(登革热病毒)的活性。DFV)、正粘病毒科(A型流感病毒,fluV-A)、副粘病毒科(呼吸道合胞病毒,RSV、2型副流感病毒,PfluV-2和犬瘟热病毒,CDV)和慢病毒科(1型人免疫缺陷病毒,HIV-1)家族。在所检测的七种多钨酸盐中,PM-43 {K-5[SiVW 11 O 40]}、PM-47 {K-7[BVV 11 O 40]}和PM-1001 [K 10 Na(VO)(3)(SbW 9 O 33)(2)] 26 H(2)O含有钒。PM-1002与PM-1001具有相同的核心结构(VO)(3)(SbW 9 O33)(2),但PM-1001的三个V原子由两个V-IV和一个V-V组成,PM-1002的三个V原子由三个V-IV组成。另一方面,PM-518 {[Et 2NH 2](7)[PTi 2 W10 O 40]}、PM-520 [Pri(2)NH(2)](5)[PTiW 11 O 40]和PM-523 [Pri NH(3)](6)H[PTi 2 W10 O38(O-2)(2)]H2O都含有钛。除了PM-43、PM-518和PM-523在大于或等于50 μ M时对PfluV-2不显示抑制活性外,所有化合物对所有检测的病毒均显示广谱抗病毒活性。分别为CDV和DFV。所有的化合物在小于2.0 μ M的EC 50下对HIV复制具有抑制作用。其中,PMs-1001和PMs-1002的抑制作用最强。该化合物在200 μ M的浓度下对MDCK、HEp-2和Vero细胞没有毒性。对于指数生长的MT-4细胞,含钒的多氧六酸盐(PM-43、47、1001、1002)在41和47 μ M之间的浓度下显示毒性。另一方面,含钛的聚氧乙烯酸盐(PM-518,-520,-523)在100 μ M时没有毒性。分析了PM-1001的抗HIV作用机制:影响HIV与细胞膜的结合和感染细胞与未感染细胞之间合胞体的形成。(C)2003 Elsevier Science B. V.保留所有权利。
Seven polyoxotungstates substituted with vanadium or titanium atoms were examined for their activity against Flaviviridae (Dengue fever virus. DFV), Orthomyxoviridae (influenza virus type A, fluV-A), Paramyxoviridae (respiratory syncytial virus, RSV, parainfluenza virus type 2, PfluV-2 and canine distemper virus, CDV) and Lentiviridae (human immunodeficiency virus type 1, HIV-1) families. Among the seven polyoxotungstates examined, PM-43 {K-5[SiVW11O40]}, PM-47 {K-7[BVW11O40]}, and PM-1001 [K10Na(VO)(3)(SbW9O33)(2)]26H(2)O contained vanadium. PM-1002 had the same core structure of (VO)(3)(SbW9O33)(2) as PM-1001; however, three V atoms of PM-1001 consisted of two V-IV and one V-V and those of PM-1002 consisted of three V-IV. On the other hand, PM-518 {[Et2NH2](7)[PTi2W10O40]}, PM-520 [Pri(2)NH(2)](5)[PTiW11O40] and PM-523 [PriNH(3)](6)H[PTi2W10O38(O-2)(2)]H2O all contained titanium. All compounds showed broad spectrum antiviral activity against all viruses examined except for PMs-43, -518 and -523 which did not exhibit inhibitory activity at greater than or equal to50 muM against PfluV-2. CDV and DFV, respectively. All compounds were inhibitory against HIV replication at an EC50 of less than 2.0 muM. Among them, PMs-1001 and -1002 showed the most potent inhibition. The compounds were not toxic for MDCK, HEp-2 and Vero cells at a concentration of 200 muM. For the exponentially growing MT-4 cells, the vanadium containing polyoxometalates (PMs-43, 47, 1001, 1002) showed toxicity at concentrations between 41 and 47 muM. On the other hand, titanium containing polyoxometalates (PMs-518, -520,-523) were not toxic at 100 muM. The mechanism of anti-HIV action of PM-1001 was analyzed: it affected the binding of HIV to the cell membrane and syncytium formation between HIV-infected and uninfected cells. (C) 2003 Elsevier Science B.V. All rights reserved.