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Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors.

Publication ,  Journal Article
Dang, Z; Xie, H; Zhu, L; Zhang, Q; Li, Z; Huang, L; Chen, C-H
Published in: ACS Med Chem Lett
November 9, 2017

As a step toward developing novel anti-HIV agents, we have identified a class of quinolizidines, including aloperine, that inhibit HIV at 1-5 μM by blocking viral entry. In this study, we have optimized the structure of aloperine and derived compounds with markedly improved activity. Our structural optimization has yielded an aloperine derivative 19 with approximately a 15-fold increase in anti-HIV-1 activity. Our mechanism of action study reveals that compound 19 does not inhibit binding of HIV-1 to receptors but arrests the virus from fusion with the membrane. Binding of the compound to HIV-1gp120 might be responsible for its anti-HIV-1 entry activity.

Duke Scholars

Published In

ACS Med Chem Lett

DOI

ISSN

1948-5875

Publication Date

November 9, 2017

Volume

8

Issue

11

Start / End Page

1199 / 1203

Location

United States

Related Subject Headings

  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0305 Organic Chemistry
  • 0304 Medicinal and Biomolecular Chemistry
 

Citation

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ICMJE
MLA
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Dang, Z., Xie, H., Zhu, L., Zhang, Q., Li, Z., Huang, L., & Chen, C.-H. (2017). Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors. ACS Med Chem Lett, 8(11), 1199–1203. https://doi.org/10.1021/acsmedchemlett.7b00376
Dang, Zhao, Hua Xie, Lei Zhu, Qingye Zhang, Zhijun Li, Li Huang, and Chin-Ho Chen. “Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors.ACS Med Chem Lett 8, no. 11 (November 9, 2017): 1199–1203. https://doi.org/10.1021/acsmedchemlett.7b00376.
Dang Z, Xie H, Zhu L, Zhang Q, Li Z, Huang L, et al. Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors. ACS Med Chem Lett. 2017 Nov 9;8(11):1199–203.
Dang, Zhao, et al. “Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors.ACS Med Chem Lett, vol. 8, no. 11, Nov. 2017, pp. 1199–203. Pubmed, doi:10.1021/acsmedchemlett.7b00376.
Dang Z, Xie H, Zhu L, Zhang Q, Li Z, Huang L, Chen C-H. Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors. ACS Med Chem Lett. 2017 Nov 9;8(11):1199–1203.
Journal cover image

Published In

ACS Med Chem Lett

DOI

ISSN

1948-5875

Publication Date

November 9, 2017

Volume

8

Issue

11

Start / End Page

1199 / 1203

Location

United States

Related Subject Headings

  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0305 Organic Chemistry
  • 0304 Medicinal and Biomolecular Chemistry