THE INHIBITION OF THE REVERSE-TRANSCRIPTASE OF HIV-1 BY THE NATURAL SULFOGLYCOLIPIDS FROM CYANOBACTERIA - CONTRIBUTION OF DIFFERENT MOIETIES TO THEIR HIGH POTENCY

The potent in vitro inhibition of the enzymatic activity of the human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT) by the lip ophilic extracts of cyanobacteria(8) was primarily attributed to the s ulfoquinovosylpranosyl lipids, compounds 1-4. These sulfolipids inhibi t efficiently and selectively only the DNA polymerase activity of HIV- 1 RT (and not the ribonuclease H function) with 50% inhibitory concent ration value (IC50) as low as 24 nM exhibited by compound 1. The novel natural compound 4, in which two hydroxy groups on the sugar moiety a re substituted by palmitoyl residues, exhibits a significant decrease in the maximal inhibition capacity. It is possible, therefore, that th e contribution of acylated groups to the molecule at these positions i nterferes with inhibition, possibly, by steric hindrance. Both the sul fonic acid moiety and the fatty acid ester side chain have a substanti al effect in potentiating the extent of inhibition. For one, the inhib itory effects of all the natural glycolipids tested (5-8) are markedly reduced, and the hydrolysis of the fatty acid side chain, as in deriv ative 9, has substantially abolished the inhibition of HIV RT.