Synthesis and Antiviral and Fungicidal Activity Evaluation of β-Carboline, Dihydro-β-carboline, Tetrahydro-β-carboline Alkaloids, and Their Derivatives
Synthesis and Antiviral and Fungicidal Activity Evaluation of β-Carboline, Dihydro-β-carboline, Tetrahydro-β-carboline Alkaloids, and Their Derivatives
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β-咔啉、二氢-β-咔啉、四氢-β-咔啉生物碱及其衍生物的合成及抗病毒和杀菌活性评价
DOI：
10.1021/jf404840x
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发表时间：
2014-02-05
影响因子：
6.1
通讯作者：
Wang, Qingmin
中科院分区：
文献类型：
--
作者：
Song, Hongjian;Liu, Yongxian;Wang, Qingmin
首次设计、合成了6种已知的β-咔啉、二氢-β-咔啉和四氢-β-咔啉生物碱及其衍生物，并对其抗烟草花叶病毒（TMV）和杀菌活性进行了评价。所有的生物碱及其衍生物（化合物3、4、14和19）在体外和体内均表现出比商业抗病毒药利巴韦林更高的抗TMV活性。特别是，生物碱Harmalan（500 μ g/mL时为62.3、55.1和60.3%）和四氢哈尔烷（500 μ g/mL时为64.2、57.2和59.5%）在体内的灭活、治疗和保护活性远高于利巴韦林（500 μ g/mL时为37.4、36.2和38.5%）。一个新的衍生物，14，具有优化的物理化学性质，在体内表现出明显更高的活性（50.4，43.9，47.9%，在500 μ g/mL）比利巴韦林和其他衍生物，因此，14可以作为一个新的先导结构的开发抗TMV药物。此外，大部分化合物对14种真菌均表现出较好的杀菌活性，其中化合物4、7和11的活性最好。
Six known beta-carboline, dihydro-beta-carboline, and tetrahydro-beta-carboline alkaloids and a series of their derivatives were designed, synthesized, and evaluated for their anti-tobacco mosaic virus (TMV) and fungicidal activities for the first time. All of the alkaloids and some of their derivatives (compounds 3, 4, 14, and 19) exhibited higher anti-TMV activity than the commercial antiviral agent Ribavirin both in vitro and in vivo. Especially, the inactivation, curative, and protection activities of alkaloids Harmalan (62.3, 55.1, and 60.3% at 500 mu g/mL) and tetrahydroharmane (64.2, 57.2, and 59.5% at 500 mu g/mL) in vivo were much higher than those of Ribavirin (37.4, 36.2, and 38.5% at 500 mu g/mL). A new derivative, 14, with optimized physicochemical properties, obviously exhibited higher activities in vivo (50.4, 43.9, and 47.9% at 500 mu g/mL) than Ribavirin and other derivatives; therefore, 14 can be used as a new lead structure for the development of anti-TMV drugs. Moreover, most of these compounds exhibited good fungicidal activity against 14 kinds of fungi, especially compounds 4, 7, and 11.