Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase

  • Bioorg Med Chem Lett. 2015 Aug 15;25(16):3168-71. doi: 10.1016/j.bmcl.2015.05.099.
Robert J Visalli  1 ,  Hannah Ziobrowski  1 ,  Kameswara R Badri  2 ,  Johnny J He  3 ,  Xiugen Zhang  3 ,  Sri Ranjini Arumugam  2 ,  Hua Zhao  4
Affiliations
  • 1. Department of Biomedical Sciences, Mercer University School of Medicine, 4700 Waters Ave., Savannah, GA 31404, USA.
  • 2. Department of Biology, Savannah State University, Savannah, GA 31404, USA.
  • 3. Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
  • 4. Department of Chemistry and Forensic Science, Savannah State University, 3219 College Street, Savannah, GA 31404, USA. Electronic address: [email protected].
PMID: 26112446 DOI: 10.1016/j.bmcl.2015.05.099
Abstract

Betulinic acid (1) has been modified to ionic derivatives (2-5) to improve its water solubility and biological activities. The binding properties of these derivatives with respect to human serum albumin (HSA) was examined and found to be similar to current anti-HIV drugs. These compounds did not inhibit HIV Reverse Transcriptase, however, 1, 2 and 5 inhibited herpes simplex type 2 (HSV-2) replication at concentrations similar to those reported for acyclovir (IC50 ∼ 0.1-10 μM) and with minimal cellular cytotoxicity. IC50 values for Antiviral activity against HSV-2 186 were 1.6, 0.6, 0.9, 7.2, and 0.9 μM for compounds 1-5, respectively.

Keywords
Betulinic acid; HIV-1 reverse transcriptase; Herpes simplex type 2 (HSV-2); Inhibitor.