Inhibitory effect of carnosic acid on HIV-1 protease in cell-free assays [corrected].
In order to find new effective HIV protease inhibitors, two diterpenes (carnosic acid [1] and carnosol [5]) were isolated from rosemary (Rosmarinus officinalis L.), and rosmanol [2] and semisynthetic derivatives (7-O-methylrosmanol [3], 7-O-ethylrosmanol [4], and 11,12-O,O-dimethylcarnosol [6]) were prepared. The inhibitory activity of all six compounds against HIV-1 protease was tested. The carnosic acid [1] showed the strongest inhibitory effect (IC90 = 0.08 micrograms/ml). The same compound was also assayed against HIV-1 virus replication (IC90 = 0.32 micrograms/ml). The cytotoxic TC90 on H9 lymphocytes was 0.36 micrograms/ml, which is very close to the effective antiviral dose. Additionally, the tested compounds did not inhibit cellular aspartic proteases cathepsin D and pepsin at the concentration range up to 10 micrograms/ml [corrected].
Paris
A
A
Department of Biochemistry, Jozef Stefan Institute, Ljubljana, Slovenia.
Strukelj
B
B
Renko
M
M
Turk
V
V
Pukl
M
M
Umek
A
A
Korant
B D
BD
D045784:Abietanes; D000818:Animals; D002402:Cathepsin D / Q000037:antagonists & inhibitors; D002417:Cattle; D002474:Cell-Free System / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D010434:Pepsin A / Q000037:antagonists & inhibitors; D010616:Phenanthrenes / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
D045784:Abietanes; D017320:HIV Protease Inhibitors; D010616:Phenanthrenes; C068623:carnosol; D010434:Pepsin A; D002402:Cathepsin D