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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Dang, Z; Zhu, L; Xie, L; Lee, K-H; Malik, F; Li, Z; Huang, L; Chen, C-H

Published Date

  • 2021

Published In

Volume / Issue

  • 28 / 24

Start / End Page

  • 4995 - 5003

PubMed ID

  • 33372864

Pubmed Central ID

  • PMC8711797

Electronic International Standard Serial Number (EISSN)

  • 1875-533X

Digital Object Identifier (DOI)

  • 10.2174/0929867328666201229121802


  • eng

Conference Location

  • United Arab Emirates