The essential oil of Ridolfia segetum (L.) Moris collected in Sardinia (Italy) has been fractionated and assayed on the two enzymatic associated activities of the HIV-1 reverse transcriptase (RT): the RNA-dependent DNA polymerase (RDDP) and the ribonuclease H (RNase-H) activities. The R. segetum oil inhibited the HIV-1 RT RDDP associated activity in a dose dependent manner showing an IC50 value of 0.094 mg/ml , while it was inactive on the RNase-H associated activity. Nevirapine was used as a positive control. Three main fractions (RS1, RS2, and RS3) were obtained from R. segetum essential oil fractionation, representing 79%, 7%, and 2%, respectively, of the total oil. The most potent fraction was RS2, containing dillapiol, myristicin and piperitenone oxide, followed by RS3 and RS1. Because these data might fit with the presence of dillapiol in the fractions, we hypothesized that this compound could exert inhibitory activity. Fraction RS2 was refractionated to obtain a mixture of dillapiol and myristicin accounting of 3,14 %of the total oil (RS-Ag). The RS‑Ag fraction was also active toward RDDP activity. Furthermore, purified dillapiol and myristicin were tested on RDDP activity and were found to inhibit it with IC50 values of 0.69 and 4.5 mg/mL, respectively. It is worth noting that both RS2 and RS‑Ag were roughly 5- to 6-fold more active than the pure dillapiol itself. A possible explanation for this finding is that dillapiol and myristicin could act synergistically on HIV-1 RT RDDP activity
