Abstract
Background: We have previously reported that a quinolizidine natural product, aloperine, and its analogs can inhibit influenza virus and/or HIV-1 at low μM concentrations.
Objective: The main goal of this study was to further optimize aloperine for improved anti-influenza virus activity.
Methods: Structural modifications have been focused on the N12 position of aloperine scaffold. Conventional chemical synthesis was used to obtain derivatives with improved antiviral activities. The anti-HIV and anti-influenza virus activities of the synthesized compounds were determined using an MT4 cell-based HIV-1 replication assay and an anti- influenza virus infection of MDCK cell assay, respectively.
Results: Aloperine derivatives can be classified into three activity groups: those that exhibit anti-HIV activity only, anti–influenza virus only, or activity against both viruses. Aloperine optimized for potent anti-influenza activity often lost anti-HIV-1 activity, and vice versa. Compound 19 inhibited influenza virus PR8 replication with an IC50 of 0.091 μM, which is approximately 160- and 60-fold more potent than aloperine and the previously reported aloperine derivative compound 3, respectively.
Conclusion: The data suggest that aloperine is a privileged scaffold that can be modified to become a selective antiviral compound with markedly improved potency against influenza virus or HIV-1.
Keywords: Aloperine, privileged scaffold, influenza A virus, HIV-1, quinolizidine derivatives, HIV-1 inhibitors.
Current Medicinal Chemistry
Title:Design and Synthesis of Quinolizidine Derivatives as Influenza Virus and HIV-1 Inhibitors
Volume: 28 Issue: 24
Author(s): Zhao Dang, Lei Zhu, Lan Xie, Kuo-Hsiung Lee, Faisal Malik, Zhijun Li, Li Huang*Chin-Ho Chen*
Affiliation:
- Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710,United States
- Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710,United States
Keywords: Aloperine, privileged scaffold, influenza A virus, HIV-1, quinolizidine derivatives, HIV-1 inhibitors.
Abstract:
Background: We have previously reported that a quinolizidine natural product, aloperine, and its analogs can inhibit influenza virus and/or HIV-1 at low μM concentrations.
Objective: The main goal of this study was to further optimize aloperine for improved anti-influenza virus activity.
Methods: Structural modifications have been focused on the N12 position of aloperine scaffold. Conventional chemical synthesis was used to obtain derivatives with improved antiviral activities. The anti-HIV and anti-influenza virus activities of the synthesized compounds were determined using an MT4 cell-based HIV-1 replication assay and an anti- influenza virus infection of MDCK cell assay, respectively.
Results: Aloperine derivatives can be classified into three activity groups: those that exhibit anti-HIV activity only, anti–influenza virus only, or activity against both viruses. Aloperine optimized for potent anti-influenza activity often lost anti-HIV-1 activity, and vice versa. Compound 19 inhibited influenza virus PR8 replication with an IC50 of 0.091 μM, which is approximately 160- and 60-fold more potent than aloperine and the previously reported aloperine derivative compound 3, respectively.
Conclusion: The data suggest that aloperine is a privileged scaffold that can be modified to become a selective antiviral compound with markedly improved potency against influenza virus or HIV-1.
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Cite this article as:
Dang Zhao, Zhu Lei, Xie Lan , Lee Kuo-Hsiung , Malik Faisal, Li Zhijun, Huang Li *, Chen Chin-Ho *, Design and Synthesis of Quinolizidine Derivatives as Influenza Virus and HIV-1 Inhibitors, Current Medicinal Chemistry 2021; 28 (24) . https://dx.doi.org/10.2174/0929867328666201229121802
DOI https://dx.doi.org/10.2174/0929867328666201229121802 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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