流感病毒和HIV-1抑制剂喹诺嗪衍生物的设计与合成

Title:Design and Synthesis of Quinolizidine Derivatives as Influenza Virus and HIV-1 Inhibitors

Volume: 28 Issue: 24

关键词: Aloperine，privileged scaffold，A型流感病毒，HIV-1，喹啉衍生物，HIV-1抑制剂。

摘要:

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.

Cite this article as:

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