NONPEPTIDE INHIBITORS OF HIV-1 PROTEASE - SYNTHESIS AND STRUCTURAL EVALUATION OF SYMMETRICAL AND NONSYMMETRICAL NAPHTHALENESULFONIC ACID ANALOGS

In this study, several representative symmetric and non-symmetric naph thalenesulfonic acid derivatives belonging to various structural class es were evaluated for their potential to inhibit HIV-1 protease. The m ost active compounds were non-symmetrical and possessed hydrophobic pe ndant groups. In general, the activity of these derivatives was depend ent on the number and position of the sulfonic acid moiety and the nat ure of the appendages. Remarkably, one of the most active compounds al so displayed inhibition of DNA polymerase and RNase H activities of HI V-1 reverse transcriptase. This observation provides an insight into d esigning singular compounds which could inhibit multiple essential enz ymes in the HIV-1 life cycle. Since it is unlikely that these agents w ill reach targeted cellular enzymes due to their polar nature, the dis covery of in vitro protease inhibition rationalizes further modificati on of sulfonic acid derivatives.