Abstract
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].
