TY - JOUR
T1 - Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase
AU - Visalli, Robert J.
AU - Ziobrowski, Hannah
AU - Badri, Kameswara R.
AU - He, Johnny J.
AU - Zhang, Xiugen
AU - Arumugam, Sri Ranjini
AU - Zhao, Hua
N1 - Funding Information:
HZ acknowledges support by the Henry Dreyfus Teacher-Scholar Award (2012), NIH MBRS-RISE grant ( 1R25GM096956 ), NIH NIBIB contract award ( HHSN268201200011C ), and National Natural Science Foundation of China – China ( 21328601 ). RJV acknowledges the support of Mercer University School of Medicine.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/7/3
Y1 - 2015/7/3
N2 - 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.
AB - 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.
KW - Betulinic acid
KW - HIV-1 reverse transcriptase
KW - Herpes simplex type 2 (HSV-2)
KW - Inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84934822156&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2015.05.099
DO - 10.1016/j.bmcl.2015.05.099
M3 - Article
C2 - 26112446
AN - SCOPUS:84934822156
SN - 0960-894X
VL - 25
SP - 3168
EP - 3171
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 16
M1 - 22789
ER -