Anti-AIDS agents 73: structure-activity relationship study and asymmetric synthesis of 3-O-monomethylsuccinyl-betulinic acid derivatives.
3-O-3'(or 2')-Methylsuccinyl-betulinic acid (MSB) derivatives were separated by using recycle HPLC. The structures of four isomers were assigned by NMR and asymmetric synthesis. 3-O-3'S-Methylsuccinyl-betulinic acid (3'S-MSB, 4) exhibited potent anti-HIV activity with an EC(50) value of 0.0087microM and a TI value of 6.3x10(3), which is comparable to the data for bevirimat (DSB, PA-457), a current clinical trials drug that was also derived from betulinic acid. The anti-HIV potency of 4 was slightly better than that of AZT.
Qian
Keduo
K
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Nakagawa-Goto
Kyoko
K
Yu
Donglei
D
Morris-Natschke
Susan L
SL
Nitz
Theodore J
TJ
Kilgore
Nicole
N
Allaway
Graham P
GP
Lee
Kuo-Hsiung
KH
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013386:Succinates / Q000138:chemical synthesis* / Q000494:pharmacology; D014315:Triterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D053978:Pentacyclic Triterpenes
D019380:Anti-HIV Agents; D013386:Succinates; D014315:Triterpenes; C479935:bevirimat; D053978:Pentacyclic Triterpenes