. In this proposal, it is demonstrated that several aqueous and organic fractions from plants used in Bolivian folk medicine have anti-HIV activity. These fractions will be further purified using various chemical techniques. Compounds will be partitioned against organic solvents based on polarity and acid/base properties. Groups of similar compounds will be further purified by chromatographic means until pure compounds are obtained. Chemical structures will be determined by nuclear magnetic resonance, mass spectrometry, or other chemical or instrumental means. The methods of action of anti-HIV compounds will be characterized in in vitro assays. Assays for the inhibition of the gp120-CD4 interaction (receptor binding), uncoating, or reverse transcriptase activity will be performed. Additional studies to evaluate whether the compounds induce the production of interferon or inhibit cellular processes, such as glycosylation, will be examined. Once purified compounds are discovered and their modes of action have been defined, the drugs will be tested for anti-HIV activity in human mononuclear cells in vitro and in an animal model for HIV infection in vivo. The investigators claim that these studies have already lead to the discovery of anti-HIV activity in several crude fractions. Further, the applicants believe that with further purification, it is possible that medicinally important anti-HIV agents may be discovered thus improving our ability to treat HIV infections in humans.
| Robinson Jr, W E; Reinecke, M G; Abdel-Malek, S et al. (1996) Inhibitors of HIV-1 replication [corrected;erratum to be published] that inhibit HIV integrase. Proc Natl Acad Sci U S A 93:6326-31 |
| Robinson Jr, W E; Cordeiro, M; Abdel-Malek, S et al. (1996) Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: inhibition of the core catalytic domain of human immunodeficiency virus integrase. Mol Pharmacol 50:846-55 |
| Abdel-Malek, S; Bastien, J W; Mahler, W F et al. (1996) Drug leads from the Kallawaya herbalists of Bolivia. 1. Background, rationale, protocol and anti-HIV activity. J Ethnopharmacol 50:157-66 |
| Robinson Jr, W E; Gorny, M K; Xu, J Y et al. (1991) Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro. J Virol 65:4169-76 |
