详情页 - 广东省中医院知识库

当前位置：首页 > 详情页

Design, synthesis, and structure activity relationship analysis of new betulinic acid derivatives as potent HIV inhibitors.

文献详情

资源类型：

Pubmed体系：

作者：

机构： [a]School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China [b]Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599-7568, USA [c]Duke University Medical Center, Box 2926, Surgical Oncology Research Facility, Durham, NC, 27710, USA [d]Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan

出处：

DOI：

ISSN：

关键词： Betulinic acid Anti-HIV inhibitor Structure-activity relationship (SAR) Quantitative SAR

摘要：

Prior modification of betulinic acid (1), a natural product lead with promising anti-HIV activity, produced 3-O-(3',3'-dimethylsuccinyl)betulinic acid (bevirimat, 3), the first-in-class HIV maturation inhibitor. After 3-resistant variants were found during Phase I and IIa clinical trials, further modification of 3 produced 4 with improved activity against wild-type and 3-resistant HIV-1. In continued efforts to optimize 1, 63 final products have now been designed, synthesized, and evaluated for anti-HIV-1 replication activity against HIV-1NL4-3 infected MT-4 cell lines. Five known and 21 new derivatives were as or more potent than 3 (EC50 0.065 μM), while eight new derivatives were as or more potent than 4 (EC50 0.019 μM). These derivatives feature expanded structural diversity and chemical space that may improve the antiviral activity and address the growing resistance crisis. Structure-Activity Relationship (SAR) correlations were thoroughly analyzed, and a 3D Quantitative SAR model with high predictability was constructed to facilitate further rational design and development of new potent derivatives. Copyright © 2021. Published by Elsevier Masson SAS.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2020]版：

大类 | 2 区

医学

小类 | 1 区药物化学

最新[2025]版：

大类 | 2 区医学

小类 | 1 区药物化学

第一作者：

第一作者机构： [a]School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China [b]Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599-7568, USA [*1]School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China.

通讯作者：

通讯机构： [a]School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China [b]Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599-7568, USA [d]Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan [*1]School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. [*2]Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599-7568, USA.

推荐引用方式(GB/T 7714)：

APA：

MLA：

Design, synthesis, and structure activity relationship analysis of new betulinic acid derivatives as potent HIV inhibitors.

文献详情

相关文献