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 , Chengrun TANG , Xusheng HUANG , Yun YANG , Qirun LI , Mengdi MA , Lei ZHAO , Liumeng YANG , Yadong CUI , Zhenqing ZHANG , Yongtang ZHENG , 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":"22 2","pages":"Pages 146-160"},"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 , Chengrun TANG , Xusheng HUANG , Yun YANG , Qirun LI , Mengdi MA , Lei ZHAO , Liumeng YANG , Yadong CUI , Zhenqing ZHANG , Yongtang ZHENG , 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\":\"22 2\",\"pages\":\"Pages 146-160\"},\"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}
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.
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.