Planta Med 2011; 77 - SL47
DOI: 10.1055/s-0031-1282170

Analogues of a lupane-type triterpene as potential anti-HIV agents

O Callies 1, LM Bedoya 2, A Muñoz 2, IA Jiménez 1, J Alcamí 2, IL Bazzocchi 1
  • 1Instituto Universitario de Bio-Orgánica „Antonio González“, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain
  • 2Centro Nacional de Microbiología, Instituto de Salud Carlos III, Crt. Majadahonda a Pozuelo, 28220 Majadahonda, Madrid, Spain

Infection with human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome (AIDS), continues to be ranked high on the list of the most important health issues facing the world. Although significant progress has been made since the introduction of highly active antiretroviral therapy, it has also led to increased adverse effects and the emergence of multidrug-resistant viral strains. Therefore, there is a need for new classes of drugs involving novel molecular mechanisms [1].

Many classes of natural products and some of their analogues have been tested for their anti-HIV activity [2]. In fact, modification of betulinic acid led to the discovery of bevirimat, a first-in-class drug candidate as a viral maturation inhibitor [3].

The goal of our study was to get new insights into the antiviral potential of lupane-type triterpenes that could inhibit HIV-1 replication and would be useful for the design of new drugs with clinical application [4]. Therefore, we prepared 17 derivatives based on the betulin scaffold, whose structures were determined by spectroscopic studies, and comparison with data previously reported. These derivatives and betulin were tested for their ability to inhibit the HIV replication. Two compounds of this series exhibited a promising activity at 10µM with replication inhibition percentages of 26 and 31%, respectively. A study of the influence of the substitution pattern on the lupane skeleton revealed that oxidation at C-3, acetylation at C-28 and modification of the isoprenyl moiety play an important role in the activity.

Keywords: Lupane triterpene; betulin analogues; anti-HIV agents

Acknowledgement: We are indebted to the Agencia Canaria de Investigación, Innovación y Sociedad de la Información (C200801000049) project for financial support. CO thanks the CajaCanarias for the fellowship.

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2. Cassels B K, Asencio M (2010) Phytochem Rev [accessible online at: http://dx.doi.org/10.1007/s11101–010–9172–2 (25 March 2010)].

3. Qian K, Kuo R-Y, Chen C-H, Huang L, Morris-Natschke SL, Lee K-H (2010)J Med Chem 53: 3233–3141.

4. Lan P et al. (2010) Med Chem Res [accessible online at: http://dx.doi.org/10.1007/s00044–010–9467–2 (21 October 2010)].