刺桐碱及其衍生物作为一类新型的HIV-1进入抑制剂
Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors.
作者信息
Dang Zhao, Zhu Lei, Lai Weihong, Bogerd Hal, Lee Kuo-Hsiung, Huang Li, Chen Chin-Ho
机构信息
Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
Department of Molecular Genetics and Microbiology, Duke University Medical Center , Durham, North Carolina 27710, United States.
出版信息
ACS Med Chem Lett. 2016 Jan 9;7(3):240-4. doi: 10.1021/acsmedchemlett.5b00339. eCollection 2016 Mar 10.
Abstract
A quinolizidine-type alkaloid aloperine was found to inhibit HIV-1 infection by blocking HIV-1 entry. Aloperine inhibited HIV-1 envelope-mediated cell-cell fusion at low micromolar concentrations. To further improve the antiviral potency, more than 30 aloperine derivatives with a variety of N12-substitutions were synthesized. Among them, 12d with an N-(1-butyl)-4-trifluoromethoxy-benzamide side chain showed the most potent anti-HIV-1 activity with EC50 at 0.69 μM. Aloperine derivatives inhibited both X4 and R5 HIV-1 Env-mediated cell-cell fusions. In addition, both BMS-806, a compound representing a class of HIV-1 gp120-targeting small molecules in clinical trials, and resistant and sensitive HIV-1 Env-mediated cell-cell fusions were equally sensitive to aloperine derivatives. These results suggest that aloperine and its derivatives are a new class of anti-HIV-1 entry inhibitors.
摘要
人们发现喹诺里西啶型生物碱阿洛哌丁通过阻断HIV-1进入来抑制HIV-1感染。阿洛哌丁在低微摩尔浓度下可抑制HIV-1包膜介导的细胞间融合。为进一步提高抗病毒效力，合成了30多种具有各种N12取代基的阿洛哌丁衍生物。其中，带有N-(1-丁基)-4-三氟甲氧基苯甲酰胺侧链的12d显示出最有效的抗HIV-1活性，其半数有效浓度（EC50）为0.69 μM。阿洛哌丁衍生物可抑制X4和R5 HIV-1包膜介导的细胞间融合。此外，在临床试验中代表一类靶向HIV-1 gp120的小分子化合物的BMS-806，以及耐药和敏感的HIV-1包膜介导的细胞间融合对阿洛哌丁衍生物同样敏感。这些结果表明，阿洛哌丁及其衍生物是一类新型的抗HIV-1进入抑制剂。
相似文献
1
Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors.刺桐碱及其衍生物作为一类新型的HIV-1进入抑制剂
ACS Med Chem Lett. 2016 Jan 9;7(3):240-4. doi: 10.1021/acsmedchemlett.5b00339. eCollection 2016 Mar 10.
2
Design and Synthesis of Quinolizidine Derivatives as Influenza Virus and HIV-1 Inhibitors.设计和合成喹诺里西啶衍生物作为流感病毒和 HIV-1 抑制剂。
Curr Med Chem. 2021;28(24):4995-5003. doi: 10.2174/0929867328666201229121802.
3
Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors.作为HIV-1进入抑制剂的阿洛哌丁衍生物的结构优化
ACS Med Chem Lett. 2017 Oct 9;8(11):1199-1203. doi: 10.1021/acsmedchemlett.7b00376. eCollection 2017 Nov 9.
4
Mutations That Increase the Stability of the Postfusion gp41 Conformation of the HIV-1 Envelope Glycoprotein Are Selected by both an X4 and R5 HIV-1 Virus To Escape Fusion Inhibitors Corresponding to Heptad Repeat 1 of gp41, but the gp120 Adaptive Mutations Differ between the Two Viruses.突变增加了 HIV-1 包膜糖蛋白 gp41 的融合后构象稳定性，被 X4 和 R5 HIV-1 病毒选择以逃避针对 gp41 七肽重复 1 的融合抑制剂，但两种病毒的 gp120 适应性突变不同。
J Virol. 2019 May 15;93(11). doi: 10.1128/JVI.00142-19. Print 2019 Jun 1.
5
Quinolizidines as Novel SARS-CoV-2 Entry Inhibitors.喹诺利嗪类化合物作为新型 SARS-CoV-2 进入抑制剂。
Int J Mol Sci. 2022 Aug 25;23(17):9659. doi: 10.3390/ijms23179659.
6
Glycosyl-Phosphatidylinositol-Anchored Anti-HIV Env Single-Chain Variable Fragments Interfere with HIV-1 Env Processing and Viral Infectivity.糖基磷脂酰肌醇锚定的抗HIV包膜单链可变片段干扰HIV-1包膜加工和病毒感染性。
J Virol. 2018 Mar 14;92(7). doi: 10.1128/JVI.02080-17. Print 2018 Apr 1.
7
Discovery and evolution of aloperine derivatives as a new family of HCV inhibitors with novel mechanism.发现和进化阿洛酮嗪衍生物作为一类新型 HCV 抑制剂，具有全新的作用机制。
Eur J Med Chem. 2018 Jan 1;143:1053-1065. doi: 10.1016/j.ejmech.2017.12.002. Epub 2017 Dec 5.
8
Activation and Inactivation of Primary Human Immunodeficiency Virus Envelope Glycoprotein Trimers by CD4-Mimetic Compounds.CD4模拟化合物对原代人免疫缺陷病毒包膜糖蛋白三聚体的激活与失活作用
J Virol. 2017 Jan 18;91(3). doi: 10.1128/JVI.01880-16. Print 2017 Feb 1.
9
Neutralization Synergy between HIV-1 Attachment Inhibitor Fostemsavir and Anti-CD4 Binding Site Broadly Neutralizing Antibodies against HIV.HIV-1 附着抑制剂福斯特玛韦与抗 CD4 结合位点广谱中和抗体对 HIV 的中和协同作用。
J Virol. 2019 Feb 5;93(4). doi: 10.1128/JVI.01446-18. Print 2019 Feb 15.
10
Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4.鉴定N-苯基-N'-(2,2,6,6-四甲基哌啶-4-基)草酰胺为一类新型的HIV-1进入抑制剂，其可阻止gp120与CD4结合。
Virology. 2005 Sep 1;339(2):213-25. doi: 10.1016/j.virol.2005.06.008.
引用本文的文献
1
The Antiviral Activity of Varenicline against Dengue Virus Replication during the Post-Entry Stage.伐尼克兰在登革病毒进入后阶段对其复制的抗病毒活性。
Biomedicines. 2023 Oct 11;11(10):2754. doi: 10.3390/biomedicines11102754.
2
Quinolizidine-Type Alkaloids: Chemodiversity, Occurrence, and Bioactivity.喹诺里西啶型生物碱：化学多样性、存在情况及生物活性。
ACS Omega. 2023 Jul 28;8(31):27862-27893. doi: 10.1021/acsomega.3c02179. eCollection 2023 Aug 8.
3
In Vitro Anti-HIV-1 Activity of Chitosan Oligomers -Conjugated with Asparagine and Glutamine.与天冬酰胺和谷氨酰胺共轭的壳寡糖的体外抗HIV-1活性
BioTech (Basel). 2023 Feb 8;12(1):18. doi: 10.3390/biotech12010018.
4
Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations.蜜蜂皂甙 I 衍生物作为成熟抑制剂的抗 HIV 潜力：合成、3D-QSAR、分子对接和分子动力学模拟。
Int J Mol Sci. 2023 Jan 11;24(2):1430. doi: 10.3390/ijms24021430.
5
Lead/Drug Discovery from Natural Resources.从自然资源中寻找先导/药物。
Molecules. 2022 Nov 28;27(23):8280. doi: 10.3390/molecules27238280.
6
Quinolizidines as Novel SARS-CoV-2 Entry Inhibitors.喹诺利嗪类化合物作为新型 SARS-CoV-2 进入抑制剂。
Int J Mol Sci. 2022 Aug 25;23(17):9659. doi: 10.3390/ijms23179659.
7
Anti-Alphaviral Alkaloids: Focus on Some Isoquinolines, Indoles and Quinolizidines.抗病毒生物碱：关注一些异喹啉类、吲哚类和喹诺里嗪类生物碱。
Molecules. 2022 Aug 10;27(16):5080. doi: 10.3390/molecules27165080.
8
The Key Role of Lysosomal Protease Cathepsins in Viral Infections.溶酶体蛋白酶组织蛋白酶在病毒感染中的关键作用。
Int J Mol Sci. 2022 Aug 13;23(16):9089. doi: 10.3390/ijms23169089.
9
Ethnobotanical Uses, Phytochemistry, Toxicology, and Pharmacological Properties of Linn. against Infectious Diseases: A Comprehensive Review.林奈氏植物在传染病防治方面的民族植物学用途、植物化学、毒理学和药理学特性：综合评价。
Molecules. 2022 Jul 8;27(14):4374. doi: 10.3390/molecules27144374.
10
Spirobisindole Alkaloids Exert Antiviral Activity in HIV Latently Infected Cell Lines by Targeting the NF-kB Cascade: In Vitro and In Silico Investigations.螺环异吲哚生物碱通过靶向 NF-κB 级联发挥抗 HIV 潜伏感染细胞系的抗病毒活性：体外和计算研究。
Molecules. 2022 Feb 5;27(3):1078. doi: 10.3390/molecules27031078.
本文引用的文献
1
Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial.在治疗经验丰富的个体中，HIV-1 附着抑制剂前药 BMS-663068 的安全性和疗效：AI438011 的 24 周结果，一项 2b 期、随机对照试验。
Lancet HIV. 2015 Oct;2(10):e427-37. doi: 10.1016/S2352-3018(15)00177-0. Epub 2015 Sep 1.
2
Pyrroloaryls and pyrroloheteroaryls: Inhibitors of the HIV fusion/attachment, reverse transcriptase and integrase.吡咯芳基和吡咯杂芳基：HIV融合/附着、逆转录酶和整合酶的抑制剂。
Bioorg Med Chem. 2015 Sep 1;23(17):5247-63. doi: 10.1016/j.bmc.2015.06.016. Epub 2015 Jun 14.
3
Maraviroc - A CCR5 Antagonist for the Treatment of HIV-1 Infection.马拉维若——一种用于治疗HIV-1感染的CCR5拮抗剂。
Front Immunol. 2015 Jun 5;6:277. doi: 10.3389/fimmu.2015.00277. eCollection 2015.
4
Homology models of the HIV-1 attachment inhibitor BMS-626529 bound to gp120 suggest a unique mechanism of action.与gp120结合的HIV-1附着抑制剂BMS-626529的同源模型表明了一种独特的作用机制。
Proteins. 2015 Feb;83(2):331-50. doi: 10.1002/prot.24726. Epub 2014 Dec 23.
5
Discovery of small molecular inhibitors targeting HIV-1 gp120-CD4 interaction drived from BMS-378806.源自BMS-378806的靶向HIV-1 gp120-CD4相互作用的小分子抑制剂的发现。
Eur J Med Chem. 2014 Oct 30;86:481-90. doi: 10.1016/j.ejmech.2014.09.012. Epub 2014 Sep 6.
6
Identification and synthesis of quinolizidines with anti-influenza a virus activity.具有抗甲型流感病毒活性的喹诺里西啶的鉴定与合成。
ACS Med Chem Lett. 2014 Jun 30;5(8):942-6. doi: 10.1021/ml500236n. eCollection 2014 Aug 14.
7
Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies.用于疫苗诱导中和抗体标准化评估的全球HIV-1 Env参考毒株专家组
J Virol. 2014 Mar;88(5):2489-507. doi: 10.1128/JVI.02853-13. Epub 2013 Dec 18.
8
Activity of the HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068, against CD4-independent viruses and HIV-1 envelopes resistant to other entry inhibitors.HIV-1 附着抑制剂 BMS-626529（前药 BMS-663068 的活性成分）对 CD4 非依赖性病毒和对其他进入抑制剂耐药的 HIV-1 包膜的活性。
Antimicrob Agents Chemother. 2013 Sep;57(9):4172-80. doi: 10.1128/AAC.00513-13. Epub 2013 Jun 17.
9
New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1.新型桦木酸衍生物对耐贝伐单抗的人类免疫缺陷病毒-1。
J Med Chem. 2013 Mar 14;56(5):2029-37. doi: 10.1021/jm3016969. Epub 2013 Feb 20.
10
HIV-1 entry inhibitors: recent development and clinical use.HIV-1 进入抑制剂：最新进展与临床应用。
Curr Opin Virol. 2013 Feb;3(1):51-7. doi: 10.1016/j.coviro.2012.12.002. Epub 2013 Jan 3.
Zotero 插件