Ionic Derivatives of Betulinic Acid Exhibit Strong Antiviral Activity Against Herpes Simplex Virus Type-2 (HSV-2) But Not HIV-1 Reverse Transcriptase

摘要

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.