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

Lipophilic and hydrophilic extracts of four Argentine plants (Gamochaeta simplicaulis Cabr. 1, Achyrocline flaccida Wein. D. C. 2, Eupatorium buniifolium H. et A. 3, and Phyllanthus sellowianus Muell. Arg. 4) were examined in vitro for their ability to inhibit the polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV‐1) reverse transcriptase (RT) (wild and Y181C mutant types). The active extracts were also examined as inhibitors of viral replication in HLT4LacZ‐1IIIB cell cultures, evaluating their cytotoxicity in parallel. Infusions 2I and 4I, among the crude extracts, showed the highest activity. These extracts were refractioned into four fractions; 2I4 and 4I4 were active as inhibitors of DNA‐polymerase (wild and Y181C types) and RNase H activities. These fractions were potent as inhibitors of viral replication and were not cytotoxic. Refractionation of 2I4 yielded five new fractions, two of which, 2I4‐4 and 2I4‐5, showed notable activity. Refractionation of 4I4 yielded four new fractions; of these, 4I4‐3 and 4I4‐4 were active. The marked biological 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 © 1999 John Wiley & Sons, Ltd.