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Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity.

Publication ,  Journal Article
Wu, H; Ma, G; Yang, Q; Zhu, Y; Huang, L; Tian, Y; Yang, X; Zhang, M; Chen, C-H; Morris-Natschke, SL; Yang, M; Xu, X; Lee, K-H
Published in: Eur J Med Chem
March 15, 2019

In this study, 12 known cycloartane triterpenoids (1-12) with four different skeletons isolated from the roots of Souliea vaginata were screened for the first time for in vitro anti-HIV activity using AZT as a standard. Among the compounds, beesioside I (1) showed the highest potency against HIV-1NL4-3 with an EC50 value of 2.32 μM (CC50 > 40 μM). Preliminary structure-activity relationship (SAR) studies on 1 indicated that simple modification of its aglycone (13) could significantly influence the antiviral activity. Particularly, the introduction of an acyl group at the C-3 position of 13 led to significant improvement in both anti-HIV potency and selectivity index. Among all synthetically modified derivatives, compound 13g was the most potent compound with an EC50 value of 0.025 μM and TI value greater than 800, comparable to those of 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB, bevirimat). Other analogues exhibited strong to weak inhibition of HIV-1 replication in MT-4 cells. The length, carboxylic terminus, and C-3' dimethyl substitution of the C-3 side chain substantially affected the anti-HIV activity. Finally, compound 13g was an effective agent against HIV with high potential for further investigation.

Duke Scholars

Published In

Eur J Med Chem

DOI

EISSN

1768-3254

Publication Date

March 15, 2019

Volume

166

Start / End Page

159 / 166

Location

France

Related Subject Headings

  • Virus Replication
  • Triterpenes
  • Structure-Activity Relationship
  • Medicinal & Biomolecular Chemistry
  • HIV-1
  • Drug Design
  • Chemistry Techniques, Synthetic
  • Anti-HIV Agents
  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
 

Citation

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Wu, H., Ma, G., Yang, Q., Zhu, Y., Huang, L., Tian, Y., … Lee, K.-H. (2019). Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity. Eur J Med Chem, 166, 159–166. https://doi.org/10.1016/j.ejmech.2019.01.020
Wu, Haifeng, Guoxu Ma, Qinwen Yang, Yindi Zhu, Li Huang, Yu Tian, Xiaoming Yang, et al. “Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity.Eur J Med Chem 166 (March 15, 2019): 159–66. https://doi.org/10.1016/j.ejmech.2019.01.020.
Wu H, Ma G, Yang Q, Zhu Y, Huang L, Tian Y, et al. Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity. Eur J Med Chem. 2019 Mar 15;166:159–66.
Wu, Haifeng, et al. “Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity.Eur J Med Chem, vol. 166, Mar. 2019, pp. 159–66. Pubmed, doi:10.1016/j.ejmech.2019.01.020.
Wu H, Ma G, Yang Q, Zhu Y, Huang L, Tian Y, Yang X, Zhang M, Chen C-H, Morris-Natschke SL, Yang M, Xu X, Lee K-H. Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity. Eur J Med Chem. 2019 Mar 15;166:159–166.
Journal cover image

Published In

Eur J Med Chem

DOI

EISSN

1768-3254

Publication Date

March 15, 2019

Volume

166

Start / End Page

159 / 166

Location

France

Related Subject Headings

  • Virus Replication
  • Triterpenes
  • Structure-Activity Relationship
  • Medicinal & Biomolecular Chemistry
  • HIV-1
  • Drug Design
  • Chemistry Techniques, Synthetic
  • Anti-HIV Agents
  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry