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Synthesis and anti-HIV activity of Bif-functional triterpene derivatives

Publication ,  Journal Article
Huang, L; Yu, D; Ho, P; Lee, KH; Chen, CH
Published in: Letters in Drug Design and Discovery
October 1, 2007

We previously reported a bi-functional betulinic acid derivative, A12-2 (4), containing an optimized C-28 side chain that exhibits potent anti-HIV activity by inhibiting both HIV-1 entry and maturation. Compound 4 contains C-3 and C-28 side chains that are pharmacophores for anti-HIV maturation and entry activity, respectively. The betulinic acid core, which serves as a molecular scaffold for compound 4, is also important for anti-HIV activity. The main purposes of the present study were to investigate the structure-activity relationships (SAR) of both the C-3 side chain and scaffold of 4. Further modification of the C-3 side chain of 4 suggested that both bulkier and smaller C-3 substituents negatively impacted the anti-HIV-1 activity. SAR study of the scaffold indicated that the betulinic acid moiety of 4 could be replaced with other scaffolds while still remaining active against HIV-1 replication. Among the synthesized compounds, the most effective molecular scaffold for anti-HIV activity remained to be betulinic acid (0.0026 μM), followed by moronic acid, ursolic acid, and oleanolic acid. On the other hand, substitution of the betulinic acid moiety of 4 with glycyrrhetinic acid or lithocholic acid completely abolished anti-HIV activity. Mechanism of action studies indicated that all active terpenoid analogs of 4 retained both anti-HIV-1 entry and anti-HIV-1 maturation activities. © 2007 Bentham Science Publishers Ltd.

Duke Scholars

Published In

Letters in Drug Design and Discovery

DOI

ISSN

1570-1808

Publication Date

October 1, 2007

Volume

4

Issue

7

Start / End Page

471 / 478

Related Subject Headings

  • Medicinal & Biomolecular Chemistry
  • 3404 Medicinal and biomolecular chemistry
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 1101 Medical Biochemistry and Metabolomics
  • 0601 Biochemistry and Cell Biology
 

Citation

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Huang, L., Yu, D., Ho, P., Lee, K. H., & Chen, C. H. (2007). Synthesis and anti-HIV activity of Bif-functional triterpene derivatives. Letters in Drug Design and Discovery, 4(7), 471–478. https://doi.org/10.2174/157018007781788561
Huang, L., D. Yu, P. Ho, K. H. Lee, and C. H. Chen. “Synthesis and anti-HIV activity of Bif-functional triterpene derivatives.” Letters in Drug Design and Discovery 4, no. 7 (October 1, 2007): 471–78. https://doi.org/10.2174/157018007781788561.
Huang L, Yu D, Ho P, Lee KH, Chen CH. Synthesis and anti-HIV activity of Bif-functional triterpene derivatives. Letters in Drug Design and Discovery. 2007 Oct 1;4(7):471–8.
Huang, L., et al. “Synthesis and anti-HIV activity of Bif-functional triterpene derivatives.” Letters in Drug Design and Discovery, vol. 4, no. 7, Oct. 2007, pp. 471–78. Scopus, doi:10.2174/157018007781788561.
Huang L, Yu D, Ho P, Lee KH, Chen CH. Synthesis and anti-HIV activity of Bif-functional triterpene derivatives. Letters in Drug Design and Discovery. 2007 Oct 1;4(7):471–478.
Journal cover image

Published In

Letters in Drug Design and Discovery

DOI

ISSN

1570-1808

Publication Date

October 1, 2007

Volume

4

Issue

7

Start / End Page

471 / 478

Related Subject Headings

  • Medicinal & Biomolecular Chemistry
  • 3404 Medicinal and biomolecular chemistry
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 1101 Medical Biochemistry and Metabolomics
  • 0601 Biochemistry and Cell Biology