Synthesis and antiviral activity of β-carboline derivatives bearing a substituted carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1)
Synthesis and antiviral activity of β-carboline derivatives bearing a substituted carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1)
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DOI：
10.1016/j.ejmech.2009.07.005
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发表时间：
2009-11-01
影响因子：
6.7
通讯作者：
Sarragiotto, Maria Helena
中科院分区：
文献类型：
--
作者：
Nazari Formagio, Anelise S.;Santos, Patricia R.;Sarragiotto, Maria Helena
合成了几种在 C-3 处带有取代的碳酰肼基团的新型 1,3-二取代 β-咔啉衍生物，并评估了它们对疫苗脊髓灰质炎病毒 (VP) 和 1 型单纯疱疹病毒 (HSV-1) 的抗病毒活性。还评估了活性化合物的细胞毒性和选择性指数。在合成的衍生物中，化合物 10 和 11 对疫苗脊髓灰质炎病毒和 HSV-1 病毒均表现出有效的活性。化合物10对HSV-1病毒表现出最高的选择性指数(SI=2446.8)和较低的细胞毒性(CC50=1150.0+/-67.3μM)。病毒产量抑制测定表明，化合物10能够在病毒吸附之前和过程中抑制HSV-1噬斑形成。在化合物处理的细胞中观察到的特征性小斑块图案表明化合物 10 抑制病毒传播到邻近细胞。使用 Lipinski 规则，通过测定亲脂性、拓扑极性表面积 (TPSA)、吸收率 (% ABS) 和简单分子描述符，进行了预测新型合成 β-咔啉衍生物 ADME 性质的计算研究。 (C) 2009 Elsevier Masson SAS。版权所有。
Several novel 1,3-disubstituted beta-carboline derivatives bearing a substituted carbohydrazide group at C-3 were synthesized and evaluated for their antiviral activity against vaccinal poliovirus (VP) and herpes simplex virus type 1 (HSV-1). The cytotoxicity and selectivity index of the active compounds were also evaluated. Among the synthesized derivatives, compounds 10 and 11 displayed potent activity against both vaccinal poliovirus and HSV-1 virus. Compound 10 presented the highest selectivity index (SI = 2446.8) against HSV-1 virus and low cytotoxicity (CC50 = 1150.0 +/- 67.3 mu M). The virus yield inhibition assay showed that compound 10 was able to inhibit HSV-1 plaque formation before and during the virus adsorption. The characteristic small plaque pattern observed in compound-treated cells suggested that compound 10 inhibited viral dissemination to neighboring cells. A computational study for prediction of ADME properties of the novel synthesized beta-carbolines derivatives was performed by determination of lipophilicity, topological polar surface area (TPSA), absorption (% ABS) and simple molecular descriptors, using Lipinski's rule. (C) 2009 Elsevier Masson SAS. All rights reserved.