Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids
Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids
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DOI：
10.1016/j.bmc.2004.10.020
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发表时间：
2005-01-17
影响因子：
3.5
通讯作者：
Lee, KH
中科院分区：
文献类型：
--
作者：
Kashiwada, Y;Aoshima, A;Lee, KH
从莲叶中分离得到(+)-1(R)- coclurine(1)和(-)-1(S)- norcoclurine(3)以及槲皮素3- o - β - d -葡糖苷(4)，经鉴定具有抗hiv作用。化合物1和3具有较强的抗hiv活性，EC50值分别为0.8、125和bbb25。化合物4的效价较低（EC50为2杯/毫升）。在一项构效关系研究中，先前从莲叶和莲胚中分离出的其它苯异喹啉、阿波啡和双苯异喹啉生物碱，包括莲叶碱（14）、负莲叶碱（15）和异莲叶碱（16），对其抗hiv活性进行了评估。化合物14 ~ 16具有较强的抗hiv活性，EC50值分别为9.9、>8.6和>6.5。阿啡类生物碱Nuciferine（12）的EC50值为0.8 mug/mL， TI值为36。此外，还对人工合成的白藜芦醇类似物进行了评价。化合物1、3、12和14-16可作为进一步开发抗艾滋病药物的新先导。(C) 2004 Elsevier Ltd.版权所有。
(+)-1(R)-Coclaurine (1) and (-)-1(S)-norcoclaurine (3), together with quercetin 3-O-beta-D-glucuronide (4), were isolated from the leaves of Nelumbo nucifera (Nymphaccae), and identified as anti-HIV principles. Compounds 1 and 3 demonstrated potent anti-HIV activity with EC50 values of 0.8 and 125 and >25, respectively. Compound 4 was less potent (EC50 2 mug/mL). In a structure-activity relationship study, other benzylisoquinoline, aporphine, and bisbenzylisoquinoline alkaloids, including liensinine (14), negferine (15), and isoliensinine (16), which were previously isolated from the leaves and embryo of Nelumbo nucifera, were evaluated for anti-HIV activity. Compounds 14-16 showed potent anti-HIV activities with EC50 values of 9.9, >8.6, and >6.5, respectively. Nuciferine (12), an aporphine alkaloid, had an EC50 value of 0.8 mug/mL and TI of 36. In addition, synthetic coclaurine analogs were also evaluated. Compounds 1, 3, 12, and 14-16 can serve as new leads for further development of anti-AIDS agents. (C) 2004 Elsevier Ltd. All rights reserved.