Argentine plant extracts active against polymerase and ribonuclease H activities of HIV-1 reverse transcriptase

Lipophilic and hydrophilic extracts of four Argentine plants (Gamochaeta si mplicaulis Cabr, 1, Achyrocline flaccida Wein, D, C, 2, Eupatorium buniifol ium W, et A. 3, and Phyllanthus sellowianus Muell. Arg, 4) were examined in vitro for their ability to inhibit the polymerase and ribonuclease Ii (RNa se Ii) activities of human immunodeficiency virus type 1 (HIV-1) reverse tr anscriptase (RT) (wild and Y181C mutant types). The active extracts were al so examined as inhibitors of viral replication in HLT4LacZ-1(IIIB) cell cul tures, evaluating their cytotoxicity in parallel. Infusions 21 and 41, amon g the crude extracts, showed the highest activity. These extracts were refr actioned into four fractions; 2I(4) and 4I(4) were active as inhibitors of DNA-polymerase (wild and Y181C types) and RNase H activities. These fractio ns were potent as inhibitors of viral replication and were not cytotoxic. R efractionation of 2I(4) yielded five new fractions, two of which, 2I(4)-4 a nd 2I(4)-5, showed notable activity. Refractionation of 4I(4) yielded four new fractions; of these, 4I(4)-3 and 4I(4)-4 were active. The marked biolog ical activity found In the infusion of A. flaccida and P. sellowianus makes them sufficiently attractive to be considered in the combined chemotherapy of the disease. Copyright (C) 1999 John Wiley & Sons, Ltd.