Betulinic acid derivatives as human immunodeficiency virus type 2 (HIV-2) inhibitors.
We previously reported that [[N-[3beta-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betulinic acid derivatives were synthesized, and some of them displayed selective anti-HIV-2 activity at nanomolar concentrations. In comparison to compounds with anti-HIV-1 activity, a shorter C-28 side chain is required for optimal anti-HIV-2 activity.
Dang
Zhao
Z
Surgical Science, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Lai
Weihong
W
Qian
Keduo
K
Ho
Phong
P
Lee
Kuo-Hsiung
KH
Chen
Chin-Ho
CH
Huang
Li
L
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000094062:Betulinic Acid
D019380:Anti-HIV Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid