光稳定剂衍生物的合成与抗艾滋病毒活性

IF 4 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Chinese Journal of Natural Medicines Pub Date : 2024-02-01 DOI:10.1016/S1875-5364(24)60587-X
Xiaolei HUANG , Chengrun TANG , Xusheng HUANG , Yun YANG , Qirun LI , Mengdi MA , Lei ZHAO , Liumeng YANG , Yadong CUI , Zhenqing ZHANG , Yongtang ZHENG , Jian ZHANG
{"title":"光稳定剂衍生物的合成与抗艾滋病毒活性","authors":"Xiaolei HUANG ,&nbsp;Chengrun TANG ,&nbsp;Xusheng HUANG ,&nbsp;Yun YANG ,&nbsp;Qirun LI ,&nbsp;Mengdi MA ,&nbsp;Lei ZHAO ,&nbsp;Liumeng YANG ,&nbsp;Yadong CUI ,&nbsp;Zhenqing ZHANG ,&nbsp;Yongtang ZHENG ,&nbsp;Jian ZHANG","doi":"10.1016/S1875-5364(24)60587-X","DOIUrl":null,"url":null,"abstract":"<div><p>In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-<em>trans</em>-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(<em>trans</em>-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound <strong>3c</strong>, exhibited the most potent anti-HIV-1 activity (EC<sub>50</sub> 2.9 nmol·L<sup>−1</sup>, CC<sub>50</sub>/EC<sub>50</sub> 11 117.24) and significantly inhibited the formation of syncytium (EC<sub>50</sub> 7.0 nmol·L<sup>−1</sup>, CC<sub>50</sub>/EC<sub>50</sub> 4891.43). Moreover, compound <strong>3c</strong> is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound <strong>3c</strong> may also function as a natural activator of protein kinase C (PKC). Therefore, compound <strong>3c</strong> emerges as a potential candidate for developing new anti-HIV drugs.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and anti-HIV activities of phorbol derivatives\",\"authors\":\"Xiaolei HUANG ,&nbsp;Chengrun TANG ,&nbsp;Xusheng HUANG ,&nbsp;Yun YANG ,&nbsp;Qirun LI ,&nbsp;Mengdi MA ,&nbsp;Lei ZHAO ,&nbsp;Liumeng YANG ,&nbsp;Yadong CUI ,&nbsp;Zhenqing ZHANG ,&nbsp;Yongtang ZHENG ,&nbsp;Jian ZHANG\",\"doi\":\"10.1016/S1875-5364(24)60587-X\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-<em>trans</em>-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(<em>trans</em>-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound <strong>3c</strong>, exhibited the most potent anti-HIV-1 activity (EC<sub>50</sub> 2.9 nmol·L<sup>−1</sup>, CC<sub>50</sub>/EC<sub>50</sub> 11 117.24) and significantly inhibited the formation of syncytium (EC<sub>50</sub> 7.0 nmol·L<sup>−1</sup>, CC<sub>50</sub>/EC<sub>50</sub> 4891.43). Moreover, compound <strong>3c</strong> is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound <strong>3c</strong> may also function as a natural activator of protein kinase C (PKC). Therefore, compound <strong>3c</strong> emerges as a potential candidate for developing new anti-HIV drugs.</p></div>\",\"PeriodicalId\":10002,\"journal\":{\"name\":\"Chinese Journal of Natural Medicines\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chinese Journal of Natural Medicines\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S187553642460587X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Natural Medicines","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S187553642460587X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
引用次数: 0

摘要

在本研究中,我们在之前合成 51 种植物醇衍生物的基础上,合成了 37 种植物醇酯衍生物,并评估了它们的抗 HIV-1 活性。12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol 衍生物脱颖而出,表现出显著的抗 HIV-1 活性和抑制合胞体形成的作用。与阳性对照药物相比,这些衍生物具有更高的安全性。其中,被命名为化合物 3c 的 12-(反式-4-氟肉桂酰基)-13-癸酰基辛二醇具有最强的抗 HIV-1 活性(EC50 2.9 nmol-L-1,CC50/EC50 117.24),并能显著抑制合胞体的形成(EC50 7.0 nmol-L-1,CC50/EC50 4891.43)。此外,化合物 3c 被认为既是 HIV-1 进入抑制剂,又是 HIV-1 逆转录酶抑制剂。等温滴定量热法和分子对接研究表明,化合物 3c 还可作为蛋白激酶 C (PKC) 的天然激活剂发挥作用。因此,化合物 3c 成为开发新型抗艾滋病毒药物的潜在候选化合物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Synthesis and anti-HIV activities of phorbol derivatives

In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound 3c, exhibited the most potent anti-HIV-1 activity (EC50 2.9 nmol·L−1, CC50/EC50 11 117.24) and significantly inhibited the formation of syncytium (EC50 7.0 nmol·L−1, CC50/EC50 4891.43). Moreover, compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C (PKC). Therefore, compound 3c emerges as a potential candidate for developing new anti-HIV drugs.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Chinese Journal of Natural Medicines
Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.50
自引率
4.30%
发文量
2235
期刊介绍: The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.
期刊最新文献
Advances in intelligent mass spectrometry data processing technology for in vivo analysis of natural medicines Chiral resolution of furofuran lignans and their derivatives from the stems of Dendrobium 'Sonia' Cyclocarysaponins A–J, dammarane-type triterpenoid glycosides from the leaves of Cyclocarya paliurus Four new diarylheptanoids and two new terpenoids from the fruits of Alpinia oxyphylla and their anti-inflammatory activities Highly oxygenated clerodane furanoditerpenoids from the leaves and twigs of Croton yunnanensis
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1